Trial Outcomes & Findings for A Study of MK-0822 in Postmenopausal Women With Osteoporosis to Assess Fracture Risk (MK-0822-018) (NCT NCT00529373)

NCT ID: NCT00529373

Last Updated: 2024-06-11

Results Overview

Morphometric vertebral fractures were assessed by central adjudication on lumbar and thoracic spinal radiographs acquired at baseline and at Months 6, 12, and subsequent yearly time points. Incident fractures (i.e., occurring after baseline) in previously normal vertebral bodies and/or those occurring after baseline in previously fractured vertebral bodies (Genant semiquantitative \[SQ\] Grade 1-3) (T4 to L4) were confirmed by quantitative morphometric (QM) and either SQ or binary SQ (yes/no) methodologies. A time-to-event methodology was used to evaluate results: life-table estimates of the incidence proportion (cumulative incidence) of participants with at least one morphometric vertebral fracture were assessed at Months 6, 12, and subsequent yearly intervals; an interval-censored approach was then used to determine incidence rate (number of participants with a morphometric fracture per 100 person-years of follow-up).

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 16071 participants
• Primary outcome timeframe: Up to approximately 60 months of observation
• Results posted on: 2024-06-11

Participant Flow

Participant milestones

Measure	Odanacatib 50 mg OW Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study STARTED	8043	8028
Base Study COMPLETED	4297	3960
Base Study NOT COMPLETED	3746	4068
First Extension Study STARTED	4297	3960
First Extension Study COMPLETED	3144	2309
First Extension Study NOT COMPLETED	1153	1651
Second Extension Study STARTED	3144	2309
Second Extension Study COMPLETED	2844	2112
Second Extension Study NOT COMPLETED	300	197

Reasons for withdrawal

Measure	Odanacatib 50 mg OW Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study Adverse Event	525	470
Base Study Lack of Efficacy	16	75
Base Study Lost to Follow-up	221	208
Base Study Other Protocol Specified Criteria	19	20
Base Study Physician Decision	60	52
Base Study Protocol Violation	48	38
Base Study Withdrawal by Subject	1062	967
Base Study Did not continue into Extension	1795	2238
First Extension Study Adverse Event	162	142
First Extension Study Lack of Efficacy	65	427
First Extension Study Lost to Follow-up	41	37
First Extension Study Other	27	47
First Extension Study Physician Decision	50	45
First Extension Study Protocol Violation	16	13
First Extension Study Withdrawal by Subject	296	287
First Extension Study Disposition record non-existing	0	1
First Extension Study Discontinued after 5 years completion	208	346
First Extension Study Did not cont. into 2nd Ext (verified)	256	281
First Extension Study Did not cont. into 2nd Ext (unknown)	32	25
Second Extension Study Adverse Event	101	51
Second Extension Study Lack of Efficacy	7	15
Second Extension Study Lost to Follow-up	18	12
Second Extension Study Other	7	12
Second Extension Study Physician Decision	63	26
Second Extension Study Protocol Violation	2	1
Second Extension Study Withdrawal by Subject	97	75
Second Extension Study Status Missing	5	5

Baseline Characteristics

A Study of MK-0822 in Postmenopausal Women With Osteoporosis to Assess Fracture Risk (MK-0822-018)

Baseline characteristics by cohort

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Total n=16071 Participants Total of all reporting groups
Age, Continuous	72.8 Years STANDARD_DEVIATION 5.4 • n=5 Participants	72.9 Years STANDARD_DEVIATION 5.3 • n=7 Participants	72.8 Years STANDARD_DEVIATION 5.3 • n=5 Participants
Sex: Female, Male Female	8043 Participants n=5 Participants	8028 Participants n=7 Participants	16071 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	97 Participants n=5 Participants	88 Participants n=7 Participants	185 Participants n=5 Participants
Race (NIH/OMB) Asian	1421 Participants n=5 Participants	1411 Participants n=7 Participants	2832 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	129 Participants n=5 Participants	132 Participants n=7 Participants	261 Participants n=5 Participants
Race (NIH/OMB) White	4528 Participants n=5 Participants	4557 Participants n=7 Participants	9085 Participants n=5 Participants
Race (NIH/OMB) More than one race	1867 Participants n=5 Participants	1839 Participants n=7 Participants	3706 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Stratum Prior Vertebral Fracture	3733 Participants n=5 Participants	3737 Participants n=7 Participants	7470 Participants n=5 Participants
Stratum No Prior Vertebral Fracture	4310 Participants n=5 Participants	4291 Participants n=7 Participants	8601 Participants n=5 Participants
Bisphosphonate-Intolerant Yes	1423 Participants n=5 Participants	1447 Participants n=7 Participants	2870 Participants n=5 Participants
Bisphosphonate-Intolerant No	6615 Participants n=5 Participants	6574 Participants n=7 Participants	13189 Participants n=5 Participants
Bisphosphonate-Intolerant Data N/A	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The Full-Analysis-Set (FAS) including all randomized participants, who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study) with at least one spine radiograph on treatment (and at baseline) was used for analysis.

Morphometric vertebral fractures were assessed by central adjudication on lumbar and thoracic spinal radiographs acquired at baseline and at Months 6, 12, and subsequent yearly time points. Incident fractures (i.e., occurring after baseline) in previously normal vertebral bodies and/or those occurring after baseline in previously fractured vertebral bodies (Genant semiquantitative [SQ] Grade 1-3) (T4 to L4) were confirmed by quantitative morphometric (QM) and either SQ or binary SQ (yes/no) methodologies. A time-to-event methodology was used to evaluate results: life-table estimates of the incidence proportion (cumulative incidence) of participants with at least one morphometric vertebral fracture were assessed at Months 6, 12, and subsequent yearly intervals; an interval-censored approach was then used to determine incidence rate (number of participants with a morphometric fracture per 100 person-years of follow-up).

Outcome measures

Measure	Odanacatib 50 mg OW n=6770 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=6910 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture	1.27 Parts. w/ fracture per 100 person-years	2.74 Parts. w/ fracture per 100 person-years

PRIMARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The FAS including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study) was used for analysis.

Osteoporotic clinical hip fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Hip fractures were fractures of the proximal femur confirmed as being located in the hip (i.e., sub-region not specified; cervical, and intertrochanteric). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Time From Baseline to First Osteoporotic Clinical Hip Fracture (Adjudicated)	0.28 Parts. w/ fracture per 100 person-years	0.54 Parts. w/ fracture per 100 person-years

PRIMARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The FAS including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study) was used for analysis.

Osteoporotic non-vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Non-vertebral fractures were assessed across multiple anatomical sites including clavicle, distal femur or shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, and wrist. Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Time From Baseline to First Osteoporotic Clinical Non-Vertebral Fracture (Adjudicated)	1.85 Parts. w/ fracture per 100 person-years	2.41 Parts. w/ fracture per 100 person-years

PRIMARY outcome

Timeframe: Up to approximately 74 months of observation

Population: The FAS including all randomized participants, who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study + first extension-double blind period \[dbp\]) with at least one spine radiograph on treatment (and at baseline) was used for analysis.

Morphometric vertebral fractures were confirmed by central adjudication on lumbar and thoracic spinal radiographs acquired at baseline and at Months 6, 12, and subsequent yearly time points. Incident fractures (i.e., occurring after baseline) in previously normal vertebral bodies and/or those occurring after baseline in previously fractured vertebral bodies (Genant SQ Grade 1-3) (T4 to L4) were confirmed by QM and either SQ or binary SQ (yes/no) methodologies. A time-to-event methodology was used to evaluate results: life-table estimates of the incidence proportion (cumulative incidence) of participants with at least one morphometric vertebral fracture were assessed at Months 6, 12, and subsequent yearly intervals; an interval-censored approach was then used to determine incidence rate (number of participants with a morphometric fracture per 100 person-years of follow-up).

Outcome measures

Measure	Odanacatib 50 mg OW n=6909 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=7011 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture	1.33 Parts. w/ fracture per 100 person-years	2.74 Parts. w/ fracture per 100 person-years

PRIMARY outcome

Timeframe: Up to approximately 74 months of observation

Population: The FAS including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study + first extension-dbp) was used for analysis.

Osteoporotic clinical hip fractures was confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Hip fractures were fractures of the proximal femur confirmed as being located in the hip (i.e., sub-region not specified; cervical, and intertrochanteric). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Hip Fracture (Adjudicated)	0.29 Parts. w/ fracture per 100 person-years	0.56 Parts. w/ fracture per 100 person-years

PRIMARY outcome

Timeframe: Up to approximately 74 months of observation

Population: The FAS including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study + first extension-dbp) was used for analysis.

Osteoporotic non-vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Non-vertebral fractures were assessed across multiple anatomical sites including clavicle, distal femur and shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, and wrist. Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Non-Vertebral Fracture (Adjudicated)	1.78 Parts. w/ fracture per 100 person-years	2.41 Parts. w/ fracture per 100 person-years

PRIMARY outcome

Timeframe: Up to approximately 74 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).

An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participants with adverse events (number of participants with an event per 100 person-years of follow-up) is provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Rate of Adverse Events	97.25 Parts. with event per 100 person-years Interval 95.0 to 99.53	96.36 Parts. with event per 100 person-years Interval 94.13 to 98.63

PRIMARY outcome

Timeframe: Up to approximately 74 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).

An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participant discontinuations from treatment due to adverse events (number of participants with an event per 100 person-years of follow-up) is provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Rate of Discontinuations From Study Treatment Due to an Adverse Event	2.66 Parts. with event per 100 person-years Interval 2.48 to 2.86	2.55 Parts. with event per 100 person-years Interval 2.37 to 2.75

PRIMARY outcome

Timeframe: Baseline and once yearly, up to approximately 108 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (total hip BMD) was used for analysis (base study + first extension-dbp + second extension).

BMD was measured by dual-energy x-ray absorptiometry (DXA) at the total hip starting at screening, and at yearly intervals until the end of the study (second extension study) for all participants who entered the second extension study. Least squares (LS) means percent change in BMD from original baseline are provided through Month 108 (Year 9). At Months 96 (Year 8) and 108 (Year 9), approximately 3% or fewer participants in each treatment group had BMD data, and results at those time points should be viewed with caution. NOTE: The mean percent change in BMD from baseline in participants originally randomized to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in the base study.

Outcome measures

Measure	Odanacatib 50 mg OW n=2997 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=2212 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension + Second Extension: Percent Change From Baseline in Bone Mineral Density (BMD) Measurements of the Total Hip Month 12	3.03 Percent change Interval 2.91 to 3.14	1.08 Percent change Interval 0.95 to 1.22
Base Study + First Extension + Second Extension: Percent Change From Baseline in Bone Mineral Density (BMD) Measurements of the Total Hip Month 24	4.32 Percent change Interval 4.18 to 4.46	0.58 Percent change Interval 0.42 to 0.74
Base Study + First Extension + Second Extension: Percent Change From Baseline in Bone Mineral Density (BMD) Measurements of the Total Hip Month 36	5.60 Percent change Interval 5.43 to 5.77	0.04 Percent change Interval -0.16 to 0.24
Base Study + First Extension + Second Extension: Percent Change From Baseline in Bone Mineral Density (BMD) Measurements of the Total Hip Month 48	6.56 Percent change Interval 6.36 to 6.76	-0.74 Percent change Interval -0.97 to -0.51
Base Study + First Extension + Second Extension: Percent Change From Baseline in Bone Mineral Density (BMD) Measurements of the Total Hip Month 60	7.45 Percent change Interval 7.22 to 7.68	-1.40 Percent change Interval -1.67 to -1.13
Base Study + First Extension + Second Extension: Percent Change From Baseline in Bone Mineral Density (BMD) Measurements of the Total Hip Month 72	7.88 Percent change Interval 7.62 to 8.14	-0.01 Percent change Interval -0.31 to 0.3
Base Study + First Extension + Second Extension: Percent Change From Baseline in Bone Mineral Density (BMD) Measurements of the Total Hip Month 84	7.94 Percent change Interval 7.63 to 8.26	0.97 Percent change Interval 0.61 to 1.34
Base Study + First Extension + Second Extension: Percent Change From Baseline in Bone Mineral Density (BMD) Measurements of the Total Hip Month 96	7.87 Percent change Interval 7.38 to 8.37	1.57 Percent change Interval 1.01 to 2.13
Base Study + First Extension + Second Extension: Percent Change From Baseline in Bone Mineral Density (BMD) Measurements of the Total Hip Month 108	7.03 Percent change Interval 6.02 to 8.05	1.11 Percent change Interval -0.02 to 2.23

PRIMARY outcome

Timeframe: Up to approximately 34 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for the analysis (second extension study).

An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Outcome measures

Measure	Odanacatib 50 mg OW n=3144 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=2309 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Second Extension: Number of Participants Who Experienced an Adverse Event	2173 Participants	1587 Participants

PRIMARY outcome

Timeframe: Up to approximately 34 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (second extension study).

An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Outcome measures

Measure	Odanacatib 50 mg OW n=3144 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=2309 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Second Extension: Number of Participants Discontinuing Study Treatment Due to an Adverse Event	55 Participants	36 Participants

PRIMARY outcome

Timeframe: Baseline, Month 24

Population: The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (lumbar spine vBMD) was used for analysis (PN032-Base).

Compartment-specific effects of osteoporosis were assessed by measuring trabecular vBMD at the lumbar spine (L1 total vertebral body) using quantitative computed tomography. The percent change from baseline at Month 24 (base study) was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

Outcome measures

Measure	Odanacatib 50 mg OW n=46 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=48 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base: Percent Change From Baseline in Volumetric Bone Mineral Density (vBMD) at the Lumbar Spine Using Quantitative Computed Tomography	8.05 Percent change Interval 4.48 to 11.62	-0.87 Percent change Interval -4.37 to 2.64

PRIMARY outcome

Timeframe: Baseline, Month 60

Population: The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (lumbar spine vBMD) was used for analysis (PN032-Base + Extension).

Compartment-specific effects of osteoporosis were assessed by measuring trabecular vBMD at the lumbar spine (L1 total vertebral body) using quantitative computed tomography. The percent change from baseline at Month 60 (base study + extension study) was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

Outcome measures

Measure	Odanacatib 50 mg OW n=28 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=25 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in vBMD at the Lumbar Spine Using Quantitative Computed Tomography	14.76 Percent change Interval 7.68 to 21.83	-11.69 Percent change Interval -18.69 to -4.69

PRIMARY outcome

Timeframe: Baseline and once yearly up to 4 years

Population: The FAS for change from baseline at specific time-points including all randomized participants who took at least one dose of study medication and had the necessary baseline and on-treatment measurements available (aLBM) was used for analysis (PN035).

Sarcopenia is the age-related loss of skeletal muscle mass and associated loss of strength. Progression of sarcopenia was assessed using aLBM as measured by total body DXA. The change from baseline at yearly intervals was then assessed using a longitudinal data analysis model with terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

Outcome measures

Measure	Odanacatib 50 mg OW n=247 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=257 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Sarcopenia Substudy PN035: Change From Baseline in Appendicular Lean Body Mass (aLBM) Month 36	-0.36 kg Interval -0.45 to -0.27	-0.32 kg Interval -0.41 to -0.23
Sarcopenia Substudy PN035: Change From Baseline in Appendicular Lean Body Mass (aLBM) Month 12	-0.20 kg Interval -0.28 to -0.12	-0.18 kg Interval -0.26 to -0.1
Sarcopenia Substudy PN035: Change From Baseline in Appendicular Lean Body Mass (aLBM) Month 24	-0.19 kg Interval -0.28 to -0.1	-0.19 kg Interval -0.28 to -0.1
Sarcopenia Substudy PN035: Change From Baseline in Appendicular Lean Body Mass (aLBM) Month 48	-0.44 kg Interval -0.64 to -0.24	-0.23 kg Interval -0.44 to -0.02

PRIMARY outcome

Timeframe: Baseline and once yearly up to 4 years

Population: The FAS for change from baseline at specific time-points including all randomized participants who took at least one dose of study medication and had the necessary baseline and on-treatment measurements available (SPPB) was used for analysis (PN035).

The Short Physical Performance Battery (SPPB) Score is used to assess physical function in older persons. The SPPB consists of 3 types of physical activities: standing balance, gait speed, and chair rise. Component activities are timed and then reduced to a categorical 0 to 4 scale based on time achieved. A higher composite score (range 0 to 12) indicates an improved function level. The change from baseline at yearly intervals was then assessed using a longitudinal data analysis model with terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

Outcome measures

Measure	Odanacatib 50 mg OW n=251 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=253 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Sarcopenia Substudy PN035: Change From Baseline in Short Physical Performance Battery (SPPB) Score Month 12	0.03 Score on a scale Interval -0.16 to 0.22	-0.08 Score on a scale Interval -0.27 to 0.11
Sarcopenia Substudy PN035: Change From Baseline in Short Physical Performance Battery (SPPB) Score Month 24	-0.04 Score on a scale Interval -0.25 to 0.16	-0.19 Score on a scale Interval -0.4 to 0.02
Sarcopenia Substudy PN035: Change From Baseline in Short Physical Performance Battery (SPPB) Score Month 36	-0.18 Score on a scale Interval -0.42 to 0.06	-0.37 Score on a scale Interval -0.62 to -0.13
Sarcopenia Substudy PN035: Change From Baseline in Short Physical Performance Battery (SPPB) Score Month 48	-0.05 Score on a scale Interval -0.34 to 0.24	-0.24 Score on a scale Interval -0.55 to 0.07

PRIMARY outcome

Timeframe: Baseline and once yearly up to 4 years.

Population: The FAS for change from baseline at specific time-points including all randomized participants who took at least one dose of study medication and had the necessary baseline and on-treatment measurements available (gait speed) was used for analysis (PN035).

Gait speed is a component of the Short Physical Performance Battery (SPPB) Score. Participants are asked to walk a distance of 4 meters at their normal pace. The test is performed 2 times, and the walk done in the shortest time is used for scoring. The activity is timed and then reduced to a categorical 0 to 4 scale based on time achieved. Higher scores indicate an improved function level. The change from baseline at yearly intervals was then assessed using a longitudinal data analysis model with terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

Outcome measures

Measure	Odanacatib 50 mg OW n=249 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=252 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Sarcopenia Substudy PN035: Change From Baseline in Gait Speed Month 12	-0.02 Score on a scale Interval -0.1 to 0.06	-0.06 Score on a scale Interval -0.14 to 0.02
Sarcopenia Substudy PN035: Change From Baseline in Gait Speed Month 24	-0.02 Score on a scale Interval -0.11 to 0.07	-0.10 Score on a scale Interval -0.19 to 0.0
Sarcopenia Substudy PN035: Change From Baseline in Gait Speed Month 36	-0.09 Score on a scale Interval -0.19 to 0.02	-0.11 Score on a scale Interval -0.22 to -0.01
Sarcopenia Substudy PN035: Change From Baseline in Gait Speed Month 48	-0.15 Score on a scale Interval -0.28 to -0.02	-0.24 Score on a scale Interval -0.38 to -0.1

SECONDARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).

An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participants with adverse events (number of participants with an event per 100 person-years of follow-up) is provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Rate of Adverse Events	100.16 Parts. with event per 100 person-years Interval 97.81 to 102.6	98.65 Parts. with event per 100 person-years Interval 96.33 to 101.01

SECONDARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).

An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participant discontinuations from treatment due to adverse events (number of participants with an event per 100 person-years of follow-up) is provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Rate of Discontinuation From Study Treatment Due to an Adverse Event	2.97 Parts. with event per 100 person-years Interval 2.75 to 3.2	2.70 Parts. with event per 100 person-years Interval 2.49 to 2.92

SECONDARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The FAS including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study) was used for analysis.

Osteoporotic vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all vertebral levels (C7, T1 to T12, L1 to L5). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Time From Baseline to First Osteoporotic Clinical Vertebral Fracture (Adjudicated)	0.16 Parts. w/ fracture per 100 person-years	0.58 Parts. w/ fracture per 100 person-years

SECONDARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (height) was used for analysis (base study).

Height was measured by wall-mounted stadiometer at randomization and at yearly intervals in the base study.

Outcome measures

Measure	Odanacatib 50 mg OW n=6112 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=6231 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Yearly Rate of Height Loss	-0.13 cm/year Interval -0.14 to -0.12	-0.15 cm/year Interval -0.16 to -0.14

SECONDARY outcome

Timeframe: Baseline and once yearly, up to approximately 60 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (height loss) was used for analysis (base study).

Height was measured by wall-mounted stadiometer at randomization and at yearly intervals in the base study.

Outcome measures

Measure	Odanacatib 50 mg OW n=6095 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=6215 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Number of Participants With Height Loss of > 1 cm Up to Month 12	316 Participants	365 Participants
Base Study: Number of Participants With Height Loss of > 1 cm Up to Month 24	592 Participants	669 Participants
Base Study: Number of Participants With Height Loss of > 1 cm Up to Month 36	875 Participants	944 Participants
Base Study: Number of Participants With Height Loss of > 1 cm Up to Month 48	90 Participants	59 Participants
Base Study: Number of Participants With Height Loss of > 1 cm Up to Month 60	23 Participants	12 Participants
Base Study: Number of Participants With Height Loss of > 1 cm Overall/At any time	1022 Participants	1149 Participants

SECONDARY outcome

Timeframe: Baseline, Month 6, and once yearly, up to approximately 60 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (total hip BMD) was used for analysis (base study).

BMD was measured by DXA for all participants at the total hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study).

Outcome measures

Measure	Odanacatib 50 mg OW n=6490 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=6596 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip Month 6	1.85 Percent change Interval 1.54 to 2.16	0.53 Percent change Interval 0.24 to 0.81
Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip Month 12	2.82 Percent change Interval 2.74 to 2.91	0.33 Percent change Interval 0.25 to 0.42
Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip Month 24	3.79 Percent change Interval 3.68 to 3.9	-0.68 Percent change Interval -0.79 to -0.57
Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip Month 36	4.81 Percent change Interval 4.67 to 4.94	-1.64 Percent change Interval -1.78 to -1.5
Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip Month 48	5.39 Percent change Interval 5.04 to 5.74	-3.23 Percent change Interval -3.59 to -2.87
Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip Month 60	5.67 Percent change Interval 5.13 to 6.21	-3.82 Percent change Interval -4.4 to -3.24

SECONDARY outcome

Timeframe: Baseline, Month 6, and once yearly, approximately 60 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (lumbar spine BMD) was used for analysis (base study).

BMD was measured by DXA for all participants at the lumbar spine at randomization, Months 6, 12, and subsequent yearly intervals until the end of the study (base study). Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses.

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Outcome measures

Measure	Odanacatib 50 mg OW n=6344 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=6400 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 6	3.75 Percent change Interval 3.39 to 4.11	0.78 Percent change Interval 0.44 to 1.13
Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 12	4.67 Percent change Interval 4.56 to 4.77	0.59 Percent change Interval 0.49 to 0.7
Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 24	6.77 Percent change Interval 6.64 to 6.9	0.72 Percent change Interval 0.59 to 0.84
Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 36	8.59 Percent change Interval 8.43 to 8.74	0.75 Percent change Interval 0.59 to 0.9
Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 48	10.47 Percent change Interval 10.09 to 10.86	0.76 Percent change Interval 0.35 to 1.16
Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 60	11.49 Percent change Interval 10.82 to 12.17	0.26 Percent change Interval -0.47 to 1.0

SECONDARY outcome

Timeframe: Baseline, Month 6, and once yearly, up to approximately 60 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (femoral neck BMD) was used for analysis (base study).

BMD was measured by DXA for all participants at the femoral neck-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study).

Outcome measures

Measure	Odanacatib 50 mg OW n=6490 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=6597 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 6	2.17 Percent change Interval 1.78 to 2.55	0.68 Percent change Interval 0.3 to 1.06
Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 12	2.80 Percent change Interval 2.68 to 2.91	0.59 Percent change Interval 0.48 to 0.7
Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 24	4.01 Percent change Interval 3.88 to 4.15	-0.37 Percent change Interval -0.5 to -0.23
Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 36	5.45 Percent change Interval 5.29 to 5.61	-1.01 Percent change Interval -1.17 to -0.85
Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 48	6.15 Percent change Interval 5.74 to 6.56	-2.27 Percent change Interval -2.71 to -1.83
Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 60	6.69 Percent change Interval 6.02 to 7.36	-1.84 Percent change Interval -2.58 to -1.11

SECONDARY outcome

Timeframe: Baseline, Month 6, and once yearly, up to approximately 60 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (trochanter BMD) was used for analysis (base study).

BMD was measured by DXA for all participants at the trochanter-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study).

Outcome measures

Measure	Odanacatib 50 mg OW n=6490 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=6596 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter Month 6	2.65 Percent change Interval 2.12 to 3.18	0.91 Percent change Interval 0.43 to 1.38
Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter Month 12	4.32 Percent change Interval 4.18 to 4.46	0.82 Percent change Interval 0.68 to 0.96
Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter Month 24	6.17 Percent change Interval 6.0 to 6.34	-0.24 Percent change Interval -0.41 to -0.07
Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter Month 36	8.01 Percent change Interval 7.81 to 8.22	-1.26 Percent change Interval -1.47 to -1.05
Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter Month 48	9.46 Percent change Interval 8.92 to 10.0	-2.98 Percent change Interval -3.54 to -2.42
Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter Month 60	10.16 Percent change Interval 9.32 to 10.99	-3.65 Percent change Interval -4.55 to -2.75

SECONDARY outcome

Timeframe: Baseline and once yearly, up to approximately 60 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (distal one-third radius BMD) was used for analysis (base study).

BMD was measured by DXA at the distal one-third radius at randomization and at yearly intervals until the end of the study (base study) in an approximate 10% random subset of participants at selected sites.

Outcome measures

Measure	Odanacatib 50 mg OW n=679 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=718 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm Month 24	0.33 Percent change Interval -0.03 to 0.68	-1.02 Percent change Interval -1.37 to -0.68
Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm Month 12	0.51 Percent change Interval 0.19 to 0.82	-0.60 Percent change Interval -0.91 to -0.3
Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm Month 36	0.02 Percent change Interval -0.36 to 0.41	-1.90 Percent change Interval -2.29 to -1.52
Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm Month 48	-0.62 Percent change Interval -1.52 to 0.28	-2.82 Percent change Interval -3.76 to -1.88
Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm Month 60	0.29 Percent change Interval -1.08 to 1.66	-3.21 Percent change Interval -4.72 to -1.7

SECONDARY outcome

Timeframe: Baseline, Month 6, and once yearly, up to approximately 60 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (lumbar spine BMD) was used for analysis (base study).

BMD was measured by DXA in bisphosphonate-intolerant participants at the lumbar spine at randomization, and at yearly intervals until the end of the study (base study). Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses. Bisphosphonates are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment.

Outcome measures

Measure	Odanacatib 50 mg OW n=1116 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=1127 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine in Bisphosphonate-Intolerant Participants Month 6	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.
Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine in Bisphosphonate-Intolerant Participants Month 12	4.56 Percent change Interval 4.31 to 4.8	0.54 Percent change Interval 0.29 to 0.78
Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine in Bisphosphonate-Intolerant Participants Month 24	6.60 Percent change Interval 6.31 to 6.9	0.82 Percent change Interval 0.52 to 1.11
Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine in Bisphosphonate-Intolerant Participants Month 36	8.49 Percent change Interval 8.13 to 8.85	0.87 Percent change Interval 0.5 to 1.23
Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine in Bisphosphonate-Intolerant Participants Month 48	10.31 Percent change Interval 9.34 to 11.29	0.80 Percent change Interval -0.4 to 2.0
Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine in Bisphosphonate-Intolerant Participants Month 60	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.

SECONDARY outcome

Timeframe: Baseline, Month 6, and once yearly, up to approximately 60 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (total hip BMD) was used for analysis (base study).

BMD was measured by DXA in bisphosphonate-intolerant participants at the total hip at screening, and at yearly intervals until the end of the study (base study). Bisphosphonates are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment.

Outcome measures

Measure	Odanacatib 50 mg OW n=1127 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=1155 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip in Bisphosphonate-Intolerant Participants Month 6	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.
Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip in Bisphosphonate-Intolerant Participants Month 12	2.63 Percent change Interval 2.43 to 2.83	0.24 Percent change Interval 0.04 to 0.44
Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip in Bisphosphonate-Intolerant Participants Month 24	3.56 Percent change Interval 3.3 to 3.82	-0.64 Percent change Interval -0.9 to -0.39
Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip in Bisphosphonate-Intolerant Participants Month 36	4.45 Percent change Interval 4.14 to 4.76	-1.41 Percent change Interval -1.72 to -1.09
Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip in Bisphosphonate-Intolerant Participants Month 48	4.07 Percent change Interval 3.09 to 5.04	-4.47 Percent change Interval -5.67 to -3.27
Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip in Bisphosphonate-Intolerant Participants Month 60	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.

SECONDARY outcome

Timeframe: Baseline, Month 6, and once yearly, up to approximately 60 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (femoral neck BMD) was used for analysis (base study).

BMD was measured by DXA in bisphosphonate-intolerant participants at the femoral neck-hip at screening, and at yearly intervals until the end of the study (base study). Bisphosphonates are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment.

Outcome measures

Measure	Odanacatib 50 mg OW n=1127 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=1156 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck in Bisphosphonate-Intolerant Participants Month 6	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.
Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck in Bisphosphonate-Intolerant Participants Month 12	2.71 Percent change Interval 2.44 to 2.98	0.50 Percent change Interval 0.24 to 0.77
Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck in Bisphosphonate-Intolerant Participants Month 24	3.88 Percent change Interval 3.56 to 4.19	-0.45 Percent change Interval -0.77 to -0.13
Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck in Bisphosphonate-Intolerant Participants Month 36	5.12 Percent change Interval 4.75 to 5.5	-0.97 Percent change Interval -1.35 to -0.59
Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck in Bisphosphonate-Intolerant Participants Month 48	6.75 Percent change Interval 5.43 to 8.08	-2.32 Percent change Interval -3.96 to -0.68
Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck in Bisphosphonate-Intolerant Participants Month 60	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.

SECONDARY outcome

Timeframe: Baseline, Month 6, and once yearly, up to approximately 60 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (trochanter BMD) was used for analysis (base study).

BMD was measured by DXA in bisphosphonate-intolerant participants at the trochanter-hip at screening, and at yearly intervals until the end of the study (base study). Bisphosphonates are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment.

Outcome measures

Measure	Odanacatib 50 mg OW n=1127 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=1155 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter in Bisphosphonate-Intolerant Participants Month 6	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.
Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter in Bisphosphonate-Intolerant Participants Month 12	4.02 Percent change Interval 3.7 to 4.35	0.58 Percent change Interval 0.26 to 0.9
Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter in Bisphosphonate-Intolerant Participants Month 24	5.73 Percent change Interval 5.33 to 6.12	-0.30 Percent change Interval -0.7 to 0.1
Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter in Bisphosphonate-Intolerant Participants Month 36	7.47 Percent change Interval 6.99 to 7.94	-1.02 Percent change Interval -1.5 to -0.54
Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter in Bisphosphonate-Intolerant Participants Month 48	6.68 Percent change Interval 5.04 to 8.32	-5.07 Percent change Interval -7.09 to -3.05
Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter in Bisphosphonate-Intolerant Participants Month 60	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.

SECONDARY outcome

Timeframe: Baseline and once yearly, up to approximately 60 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (distal one-third radius BMD) was used for analysis (base study).

BMD was measured by DXA at the distal one-third radius at randomization and at yearly intervals until the end of the study (base study) in an approximate 10% random subset of bisphosphonate-intolerant participants at selected sites. Bisphosphonates are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment.

Outcome measures

Measure	Odanacatib 50 mg OW n=77 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=112 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm in Bisphosphonate-Intolerant Participants Month 12	0.99 Percent change Interval 0.06 to 1.93	-0.09 Percent change Interval -0.87 to 0.69
Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm in Bisphosphonate-Intolerant Participants Month 24	0.24 Percent change Interval -0.79 to 1.28	-0.80 Percent change Interval -1.67 to 0.06
Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm in Bisphosphonate-Intolerant Participants Month 36	-0.66 Percent change Interval -1.76 to 0.44	-1.87 Percent change Interval -2.82 to -0.92
Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm in Bisphosphonate-Intolerant Participants Month 48	-0.72 Percent change Interval -4.9 to 3.45	-2.27 Percent change Interval -7.23 to 2.68
Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm in Bisphosphonate-Intolerant Participants Month 60	—	NA Percent change Not calculated due to convergence issue with longitudinal data analysis model.

SECONDARY outcome

Timeframe: Baseline, Month 6, and once yearly up to 4 years

Population: The per-protocol population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (s-CTx) and excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (base study).

s-CTx, a biochemical marker of bone resorption by osteoclasts reflecting collagen breakdown products, was assessed at randomization, Month 6, and at yearly intervals until the end of the study (base study) in an approximate 10% random subset participants at selected sites. The log-transformed fraction from baseline in s-CTx was determined using a longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS means weighted for region and stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=618 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=629 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Percent Change From Baseline in Serum C-Telopeptides of Type I Collagen (s-CTx) After Log-Transformation Month 6	-61.27 Percent change Interval -63.33 to -59.09	-2.28 Percent change Interval -7.43 to 3.15
Base Study: Percent Change From Baseline in Serum C-Telopeptides of Type I Collagen (s-CTx) After Log-Transformation Month 12	-53.47 Percent change Interval -55.98 to -50.81	6.54 Percent change Interval 0.85 to 12.56
Base Study: Percent Change From Baseline in Serum C-Telopeptides of Type I Collagen (s-CTx) After Log-Transformation Month 24	-39.47 Percent change Interval -42.61 to -36.15	7.23 Percent change Interval 1.7 to 13.07
Base Study: Percent Change From Baseline in Serum C-Telopeptides of Type I Collagen (s-CTx) After Log-Transformation Month 36	-23.71 Percent change Interval -27.79 to -19.4	20.96 Percent change Interval 14.38 to 27.91
Base Study: Percent Change From Baseline in Serum C-Telopeptides of Type I Collagen (s-CTx) After Log-Transformation Month 48	-4.61 Percent change Interval -15.93 to 8.24	14.12 Percent change Interval 0.47 to 29.61

SECONDARY outcome

Timeframe: Baseline, Month 6, and once yearly up to 4 years

Population: The per-protocol population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (u-NTx/Cr) and excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (base study).

u-NTx, a biochemical marker of bone resorption, was assessed at randomization, Month 6, and at yearly intervals until the end of the study (base study) in an approximate 10% random subset participants at selected sites. Urine NTx measurements (in bone collagen equivalents [BCE]) were normalized to urine Cr concentration (i.e., u-NTx/Cr ratio) and the log-transformed fraction from baseline in u-NTx/Cr ratio was then determined using a longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS means weighted for region and stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=603 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=619 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Percent Change From Baseline in Urinary N-Telopeptides of Type I Collagen/Creatinine (u-NTx/Cr) Ratio After Log-Transformation Month 6	-56.46 Percent change Interval -58.27 to -54.56	-4.76 Percent change Interval -8.68 to -0.67
Base Study: Percent Change From Baseline in Urinary N-Telopeptides of Type I Collagen/Creatinine (u-NTx/Cr) Ratio After Log-Transformation Month 12	-55.58 Percent change Interval -57.54 to -53.53	-1.99 Percent change Interval -6.26 to 2.48
Base Study: Percent Change From Baseline in Urinary N-Telopeptides of Type I Collagen/Creatinine (u-NTx/Cr) Ratio After Log-Transformation Month 24	-47.21 Percent change Interval -49.7 to -44.61	9.46 Percent change Interval 4.33 to 14.85
Base Study: Percent Change From Baseline in Urinary N-Telopeptides of Type I Collagen/Creatinine (u-NTx/Cr) Ratio After Log-Transformation Month 36	-43.91 Percent change Interval -46.8 to -40.86	15.23 Percent change Interval 9.15 to 21.64
Base Study: Percent Change From Baseline in Urinary N-Telopeptides of Type I Collagen/Creatinine (u-NTx/Cr) Ratio After Log-Transformation Month 48	-38.01 Percent change Interval -46.3 to -28.43	6.53 Percent change Interval -7.38 to 22.53

SECONDARY outcome

Timeframe: Baseline, Month 6, and once yearly up to 4 years

Population: The per-protocol population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (BSAP) and excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (base study).

BSAP is an enzyme produced by matrix-synthesizing osteoblasts during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum BSAP was assessed at randomization, Month 6, and at yearly intervals until the end of the study (base study) in an approximate 10% random subset participants at selected sites. The log-transformed fraction from baseline in BSAP was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=634 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=650 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP) After Log-Transformation Month 6	-23.27 Percent change Interval -25.12 to -21.38	-9.13 Percent change Interval -11.28 to -6.93
Base Study: Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP) After Log-Transformation Month 12	-21.43 Percent change Interval -23.53 to -19.27	-9.42 Percent change Interval -11.8 to -6.97
Base Study: Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP) After Log-Transformation Month 24	-9.33 Percent change Interval -12.1 to -6.47	-0.04 Percent change Interval -3.07 to 3.08
Base Study: Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP) After Log-Transformation Month 36	-8.41 Percent change Interval -11.23 to -5.51	-0.77 Percent change Interval -3.85 to 2.4
Base Study: Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP) After Log-Transformation Month 48	-0.63 Percent change Interval -8.39 to 7.8	0.15 Percent change Interval -7.93 to 8.94

SECONDARY outcome

Timeframe: Baseline, Month 6, and once yearly up to 4 years

Population: The per-protocol population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (P1NP) and excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (base study).

P1NP is a cleavage fragment produced during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum P1NP was assessed at randomization, Month 6, and at yearly intervals until the end of the study (base study) in an approximate 10% random subset participants at selected sites. The log-transformed fraction from baseline in P1NP was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=634 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=650 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Percent Change From Baseline in N-Terminal Propeptide of Type 1 Collagen (P1NP) After Log-Transformation Month 6	-44.51 Percent change Interval -46.71 to -42.23	-15.08 Percent change Interval -18.39 to -11.65
Base Study: Percent Change From Baseline in N-Terminal Propeptide of Type 1 Collagen (P1NP) After Log-Transformation Month 12	-37.49 Percent change Interval -40.12 to -34.75	-11.55 Percent change Interval -15.21 to -7.72
Base Study: Percent Change From Baseline in N-Terminal Propeptide of Type 1 Collagen (P1NP) After Log-Transformation Month 24	-22.46 Percent change Interval -25.69 to -19.09	-6.20 Percent change Interval -10.08 to -2.16
Base Study: Percent Change From Baseline in N-Terminal Propeptide of Type 1 Collagen (P1NP) After Log-Transformation Month 36	-11.89 Percent change Interval -15.7 to -7.92	0.22 Percent change Interval -4.15 to 4.78
Base Study: Percent Change From Baseline in N-Terminal Propeptide of Type 1 Collagen (P1NP) After Log-Transformation Month 48	-3.61 Percent change Interval -12.04 to 5.62	-0.28 Percent change Interval -9.25 to 9.58

SECONDARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).

The time to first TIMI-adjudicated 3-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, or 3. non-fatal definite stroke) was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Time to First 3-Point Major Adverse Cardiac Event (MACE) Confirmed by Thrombolysis in Myocardial Infarction Study Group (TIMI) Adjudication	1.17 Parts. with event per 100 person-years	1.04 Parts. with event per 100 person-years

SECONDARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).

The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardiogram confirmation was not required. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Time to First New Onset Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication	0.48 Parts. with event per 100 person-years	0.41 Parts. with event per 100 person-years

SECONDARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).

The time to first TIMI-adjudicated 4-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, 3. non-fatal definite stroke, or 4. hospitalization for unstable angina) was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Time to First 4-Point MACE Confirmed by TIMI Adjudication	1.28 Parts. with event per 100 person-years	1.14 Parts. with event per 100 person-years

SECONDARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).

The time to first TIMI-adjudicated hospitalization for unstable angina was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Time to First Hospitalization for Unstable Angina Confirmed by TIMI Adjudication	0.10 Parts. with event per 100 person-years	0.09 Parts. with event per 100 person-years

SECONDARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).

The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardiogram confirmation was required. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Time to First New Onset ECG-Confirmed Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication	0.25 Parts. with event per 100 person-years	0.23 Parts. with event per 100 person-years

SECONDARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).

The time to first TIMI-adjudicated any reported episode of atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were included and electrocardiogram confirmation was not required. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Time to First Any Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication	0.60 Parts. with event per 100 person-years	0.48 Parts. with event per 100 person-years

SECONDARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).

The time to first TIMI-adjudicated all-cause death was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Time to First All-Cause Death Confirmed by TIMI Adjudication	1.55 Parts. with event per 100 person-years	1.38 Parts. with event per 100 person-years

SECONDARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).

The time to first TIMI-adjudicated cardiovascular death was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Time to First Cardiovascular Death Confirmed by TIMI Adjudication	0.45 Parts. with event per 100 person-years	0.39 Parts. with event per 100 person-years

SECONDARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).

The time to first TIMI-adjudicated fatal or non-fatal definite myocardial infarction was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Time to First Fatal or Non-Fatal Myocardial Infarction Confirmed by TIMI Adjudication	0.25 Parts. with event per 100 person-years	0.31 Parts. with event per 100 person-years

SECONDARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).

The time to first TIMI-adjudicated fatal definite myocardial infarction was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Time to First Fatal Myocardial Infarction Confirmed by TIMI Adjudication	0.03 Parts. with event per 100 person-years	0.03 Parts. with event per 100 person-years

SECONDARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).

The time to first TIMI-adjudicated fatal or non-fatal definite stroke was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Time to First Fatal or Non-Fatal Stroke Confirmed by TIMI Adjudication	0.58 Parts. with event per 100 person-years	0.44 Parts. with event per 100 person-years

SECONDARY outcome

Timeframe: Up to approximately 60 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).

The time to first TIMI-adjudicated fatal definite stroke was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Time to First Fatal Stroke Confirmed by TIMI Adjudication	0.09 Parts. with event per 100 person-years	0.05 Parts. with event per 100 person-years

SECONDARY outcome

Timeframe: Baseline, Month 6, and once yearly, up to approximately 74 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (femoral neck BMD) was used for analysis (base study + first extension-dbp).

BMD was measured by DXA for all participants at the femoral neck-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp).

Outcome measures

Measure	Odanacatib 50 mg OW n=6498 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=6601 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 6	2.17 Percent change Interval 1.78 to 2.55	0.70 Percent change Interval 0.32 to 1.08
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 12	2.81 Percent change Interval 2.7 to 2.92	0.60 Percent change Interval 0.49 to 0.71
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 24	4.03 Percent change Interval 3.9 to 4.16	-0.36 Percent change Interval -0.49 to -0.22
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 36	5.48 Percent change Interval 5.32 to 5.64	-1.02 Percent change Interval -1.18 to -0.86
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 48	6.37 Percent change Interval 6.17 to 6.56	-1.93 Percent change Interval -2.13 to -1.73
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 60	7.30 Percent change Interval 7.08 to 7.53	-2.75 Percent change Interval -2.99 to -2.51

SECONDARY outcome

Timeframe: Baseline and once yearly, up to approximately 74 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (distal one-third radius BMD) was used for analysis (base study + first extension-dbp).

BMD was measured by DXA at the distal one-third radius at randomization and at yearly intervals until the end of the study (base study + first extension-dbp) in an approximate 10% random subset of participants at selected sites.

Outcome measures

Measure	Odanacatib 50 mg OW n=679 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=718 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm Month 24	0.33 Percent change Interval -0.01 to 0.68	-1.02 Percent change Interval -1.37 to -0.68
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm Month 12	0.50 Percent change Interval 0.18 to 0.81	-0.61 Percent change Interval -0.91 to -0.3
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm Month 36	0.05 Percent change Interval -0.33 to 0.43	-1.91 Percent change Interval -2.29 to -1.53
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm Month 48	-0.30 Percent change Interval -0.84 to 0.23	-2.49 Percent change Interval -3.05 to -1.92
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm Month 60	-0.84 Percent change Interval -1.37 to -0.31	-3.17 Percent change Interval -3.74 to -2.59

SECONDARY outcome

Timeframe: Up to approximately 74 months of observation

Population: The FAS including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study + first extension) was used for analysis.

Osteoporotic vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all vertebral levels (C7, T1 to T12, L1 to L5). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Vertebral Fracture (Adjudicated)	0.18 Parts. with event per 100 person-years	0.56 Parts. with event per 100 person-years

SECONDARY outcome

Timeframe: Up to approximately 74 months of observation

Population: The FAS including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study + first extension) was used for analysis.

Osteoporotic clinical fractures (combining vertebral and non-vertebral) were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all vertebral levels (C7, T1 to T12, L1 to L5). Non-vertebral fractures were assessed across multiple anatomical sites including clavicle, distal femur or shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, and wrist. Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Fracture (Adjudicated)	1.95 Parts. with event per 100 person-years	2.93 Parts. with event per 100 person-years

SECONDARY outcome

Timeframe: Baseline, Month 6, and once yearly, up to approximately 74 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (total hip BMD) was used for analysis (base study + first extension-dbp).

BMD was measured by DXA for all participants at the total hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp).

Outcome measures

Measure	Odanacatib 50 mg OW n=6498 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=6601 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Total Hip Month 6	1.89 Percent change Interval 1.6 to 2.17	0.55 Percent change Interval 0.26 to 0.83
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Total Hip Month 12	2.84 Percent change Interval 2.75 to 2.92	0.34 Percent change Interval 0.26 to 0.43
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Total Hip Month 24	3.79 Percent change Interval 3.68 to 3.9	-0.67 Percent change Interval -0.78 to -0.57
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Total Hip Month 36	4.78 Percent change Interval 4.65 to 4.92	-1.67 Percent change Interval -1.81 to -1.54
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Total Hip Month 48	5.52 Percent change Interval 5.35 to 5.69	-2.97 Percent change Interval -3.14 to -2.79
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Total Hip Month 60	6.23 Percent change Interval 6.02 to 6.44	-4.06 Percent change Interval -4.28 to -3.84

SECONDARY outcome

Timeframe: Baseline, Month 6, and once yearly, up to approximately 74 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (trochanter BMD) was used for analysis (base study + first extension-dbp).

BMD was measured by DXA for all participants at the trochanter-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp).

Outcome measures

Measure	Odanacatib 50 mg OW n=6498 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=6601 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Trochanter Month 6	2.70 Percent change Interval 2.21 to 3.18	0.95 Percent change Interval 0.47 to 1.43
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Trochanter Month 12	4.33 Percent change Interval 4.19 to 4.47	0.83 Percent change Interval 0.69 to 0.97
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Trochanter Month 24	6.17 Percent change Interval 6.0 to 6.34	-0.23 Percent change Interval -0.4 to -0.06
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Trochanter Month 36	7.96 Percent change Interval 7.75 to 8.16	-1.29 Percent change Interval -1.5 to -1.08
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Trochanter Month 48	9.27 Percent change Interval 9.01 to 9.53	-2.86 Percent change Interval -3.13 to -2.59
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Trochanter Month 60	10.66 Percent change Interval 10.36 to 10.97	-3.90 Percent change Interval -4.22 to -3.57

SECONDARY outcome

Timeframe: Baseline, Month 6, and once yearly, up to approximately 74 months of observation

Population: The FAS population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (lumbar spine BMD) was used for analysis (base study + first extension-dbp).

BMD was measured by DXA for all participants at the lumbar spine at randomization, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp). Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses.

Outcome measures

Measure	Odanacatib 50 mg OW n=6220 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=6375 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 60	11.93 Percent change Interval 11.71 to 12.15	1.06 Percent change Interval 0.83 to 1.29
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 6	3.72 Percent change Interval 3.36 to 4.07	0.82 Percent change Interval 0.47 to 1.17
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 12	4.61 Percent change Interval 4.5 to 4.71	0.60 Percent change Interval 0.49 to 0.7
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 24	6.63 Percent change Interval 6.5 to 6.76	0.70 Percent change Interval 0.58 to 0.83
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 36	8.41 Percent change Interval 8.26 to 8.56	0.72 Percent change Interval 0.56 to 0.87
Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 48	10.19 Percent change Interval 10.01 to 10.38	0.85 Percent change Interval 0.66 to 1.04

SECONDARY outcome

Timeframe: Up to approximately 108 months of observation

Population: Study was terminated early due to observed increase in risk of stroke in Protocol MK-0822-018. As a result, efficacy analyses in 2nd Extension were limited to change in BMD and incidence of osteoporotic clinical fractures; Base Study + 1st Ext + 2nd Ext: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture was not analyzed.

Morphometric vertebral fractures were assessed by central adjudication on lumbar and thoracic spinal radiographs acquired at baseline (base study) and at Months 6, 12, and subsequent yearly time points. Incident fractures (i.e., occurring after baseline) in previously normal vertebral bodies and/or those occurring after baseline in previously fractured vertebral bodies (Genant semiquantitative [SQ] Grade 1-3) (T4 to L4) were confirmed by quantitative morphometric (QM) and either SQ or binary SQ (yes/no) methodologies. A time-to-event methodology was used to evaluate results: life-table estimates of the incidence proportion (cumulative incidence) of participants with at least one morphometric vertebral fracture were assessed at Months 6, 12, and subsequent yearly intervals; an interval-censored approach was then used to determine incidence rate (number of participants with a morphometric fracture per 100 person-years of follow-up).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and once yearly, up to approximately 108 months of observation

Population: Study was terminated early due to observed increase in risk of stroke in Protocol MK-0822-018. As a result, efficacy analyses in 2nd Extension were limited to change in BMD and incidence of osteoporotic clinical fractures; Base Study + First Extension + Second Extension: Change in Height from Baseline Stature was not analyzed.

Height was measured by wall-mounted stadiometer at randomization and at yearly intervals across the base study and the two extension studies.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and once yearly, up to approximately 108 months of observation

Population: The FAS population consisted of all randomized participants who entered the second extension study and received at least one dose of open-label treatment and had the necessary on-treatment information (lumbar spine BMD).

BMD was measured by DXA at the lumbar spine starting at randomization, and at yearly intervals until the end of the study (2nd extension study) for all participants who entered the 2nd extension study. Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses. At Months 96 and 108, approximately 3% or fewer participants in each treatment group had BMD data, and results at those time points should be viewed with caution. NOTE: The mean percent change in BMD from baseline in participants originally randomized to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in the base study. A longitudinal model with terms for treatment, stratum, region & interaction between treatment and time as fixed effects (LS means weighted for region & stratum size) was used for analysis.

Outcome measures

Measure	Odanacatib 50 mg OW n=2818 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=2128 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 12	4.68 Percent change Interval 4.54 to 4.83	1.01 Percent change Interval 0.84 to 1.17
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 24	6.95 Percent change Interval 6.78 to 7.12	1.40 Percent change Interval 1.21 to 1.59
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 36	8.84 Percent change Interval 8.65 to 9.04	1.61 Percent change Interval 1.39 to 1.83
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 48	10.74 Percent change Interval 10.51 to 10.97	2.06 Percent change Interval 1.8 to 2.33
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 60	12.55 Percent change Interval 12.29 to 12.81	2.45 Percent change Interval 2.16 to 2.75
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 72	13.76 Percent change Interval 13.46 to 14.06	6.25 Percent change Interval 5.91 to 6.59
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 84	14.91 Percent change Interval 14.56 to 15.26	8.37 Percent change Interval 7.97 to 8.77
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 96	15.13 Percent change Interval 14.48 to 15.78	9.66 Percent change Interval 8.95 to 10.38
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine Month 108	15.54 Percent change Interval 14.23 to 26.85	10.85 Percent change Interval 9.42 to 12.27

SECONDARY outcome

Timeframe: Baseline and once yearly, up to approximately 108 months of observation

Population: The FAS population consisted of all randomized participants who entered the second extension study and received at least one dose of open-label treatment and had the necessary on-treatment information (femoral neck BMD).

BMD was measured by DXA at the femoral neck starting at screening, and at yearly intervals until the end of the study (2nd extension study) for all participants who entered the 2nd extension study. LS means percent change in BMD from original baseline are provided through Month 108. At Months 96 and 108, approximately 3% or fewer participants in each treatment group had BMD data, and results at those time points should be viewed with caution. NOTE: The mean percent change in BMD from baseline in participants originally randomized to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in the base study. A longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS means weighted for region and stratum size) was used for analysis.

Outcome measures

Measure	Odanacatib 50 mg OW n=2997 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=2212 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 12	2.89 Percent change Interval 2.73 to 3.05	1.06 Percent change Interval 0.88 to 1.24
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 24	4.39 Percent change Interval 4.2 to 4.57	0.38 Percent change Interval 0.17 to 0.6
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 36	6.02 Percent change Interval 5.81 to 6.24	-0.03 Percent change Interval -0.28 to 0.22
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 48	7.01 Percent change Interval 6.78 to 7.25	-0.73 Percent change Interval -1.01 to -0.46
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 60	7.98 Percent change Interval 7.7 to 8.25	-1.32 Percent change Interval -1.63 to -1.0
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 72	8.51 Percent change Interval 8.21 to 8.81	0.41 Percent change Interval 0.06 to 0.76
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 84	9.11 Percent change Interval 8.75 to 9.48	1.56 Percent change Interval 1.13 to 1.98
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 96	8.84 Percent change Interval 8.22 to 9.46	1.95 Percent change Interval 1.24 to 2.65
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck Month 108	9.38 Percent change Interval 7.83 to 10.92	3.63 Percent change Interval 1.91 to 5.35

SECONDARY outcome

Timeframe: Baseline and once yearly, up to approximately 108 months of observation

Population: The FAS population consisted of all randomized participants who entered the second extension study and received at least one dose of open-label treatment and had the necessary on-treatment information (trochanter BMD).

BMD was measured by DXA at the trochanter starting at screening, and at yearly intervals until the end of the study (2nd extension study) for all participants who entered the 2nd extension study. LS means percent change in BMD from original baseline are provided through Month 108. At Months 96 and 108, approximately 3% or fewer participants in each treatment group had BMD data, and results at those time points should be viewed with caution. NOTE: The mean percent change in BMD from baseline in participants originally randomized to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in the base study. A longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS means weighted for region and stratum size) was used for analysis.

Outcome measures

Measure	Odanacatib 50 mg OW n=2997 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=2212 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Trochanter Month 12	4.55 Percent change Interval 4.34 to 4.75	1.81 Percent change Interval 1.58 to 2.05
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Trochanter Month 24	6.85 Percent change Interval 6.62 to 7.08	1.45 Percent change Interval 1.18 to 1.72
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Trochanter Month 36	9.00 Percent change Interval 8.73 to 9.28	0.89 Percent change Interval 0.57 to 1.21
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Trochanter Month 48	10.58 Percent change Interval 10.26 to 10.89	-0.16 Percent change Interval -0.52 to 0.21
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Trochanter Month 60	12.21 Percent change Interval 11.85 to 12.57	-0.68 Percent change Interval -1.09 to -0.26
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Trochanter Month 72	12.95 Percent change Interval 12.55 to 13.34	1.22 Percent change Interval 0.76 to 1.68
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Trochanter Month 84	13.30 Percent change Interval 12.82 to 13.78	3.17 Percent change Interval 2.61 to 3.73
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Trochanter Month 96	13.44 Percent change Interval 12.67 to 14.2	4.66 Percent change Interval 3.79 to 5.54
Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Trochanter Month 108	12.69 Percent change Interval 10.86 to 14.51	2.97 Percent change Interval 0.95 to 5.0

SECONDARY outcome

Timeframe: Up to approximately 34 months of observation

Population: The All-Participants-as-Treated Population including all randomized participants who entered the second extension study and received at least one dose of open-label treatment was used for analysis.

Osteoporotic vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all lumbar vertebral levels (L1 to L5). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence of participants in the second extension study with osteoporotic vertebral clinical fractures is provided. Due to early termination of the study, the cumulative incidence using a time-to-event methodology was not assessed across base and extension studies.

Outcome measures

Measure	Odanacatib 50 mg OW n=3114 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=2309 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Second Extension: Incidence of Osteoporotic Clinical Lumbar Vertebral Fracture (Adjudicated)	0.22 Percentage of Participants	0.04 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately 34 months of observation

Population: The All-Participants-as-Treated Population including all randomized participants who entered the second extension study and received at least one dose of open-label treatment was used for analysis.

Osteoporotic vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all thoracic vertebral levels (T1 to T12). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence of participants in the second extension study with osteoporotic vertebral clinical fractures is provided. Due to early termination of the study, the cumulative incidence using a time-to-event methodology was not assessed across base and extension studies.

Outcome measures

Measure	Odanacatib 50 mg OW n=3114 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=2309 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Second Extension: Incidence of Osteoporotic Clinical Thoracic Vertebral Fracture (Adjudicated)	0.13 Percentage of Participants	0.09 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately 34 months of observation

Population: The The All-Participants-as-Treated Population including all randomized participants who entered the second extension study and received at least one dose of open-label treatment was used for analysis.

Osteoporotic clinical fractures of any type were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Non-vertebral fractures were assessed across multiple anatomical sites including clavicle, distal femur or shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, and wrist; Vertebral fractures assessed across all vertebral levels (C7, T1 to T12, L1 to L5) were included in the analysis. Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence proportion (cumulative incidence) of participants in the second extension study with at least one osteoporotic clinical fracture of any type is provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=3144 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=2309 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Second Extension: Time From Baseline to First Osteoporotic Clinical Fracture of Any Type (Adjudicated)	2.04 Parts. with event per 100 person-years	2.64 Parts. with event per 100 person-years

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (total hip cortical vBMD) was used for analysis (PN032-Base).

Compartment-specific effects of osteoporosis were assessed by measuring cortical vBMD at the total hip using quantitative computed tomography. The percent change from baseline at Month 24 was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

Outcome measures

Measure	Odanacatib 50 mg OW n=51 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=55 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base: Percent Change From Baseline in Cortical vBMD of the Total Hip Using Quantitative Computed Tomography	3.29 Percent change Interval 2.33 to 4.24	0.52 Percent change Interval -0.39 to 1.44

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (lumbar spine aBMD) was used for analysis (PN032-Base).

aBMD was measured at the lumbar spine (L1 to L4) at baseline and Month 24 using DXA . If a vertebra was fractured at baseline or became fractured during the study, its BMD measurement was excluded from analysis. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

Outcome measures

Measure	Odanacatib 50 mg OW n=50 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=59 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base: Percent Change From Baseline in Areal BMD (aBMD) of the Lumbar Spine Using DXA	5.63 Percent change Interval 4.54 to 6.72	0.08 Percent change Interval -0.92 to 1.09

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (femoral neck aBMD) was used for analysis (PN032-Base).

aBMD was measured at the femoral neck at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

Outcome measures

Measure	Odanacatib 50 mg OW n=49 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=58 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Femoral Neck Using DXA	3.15 Percent change Interval 1.74 to 4.56	0.36 Percent change Interval -0.94 to 1.65

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (total hip aBMD) was used for analysis (PN032-Base).

aBMD was measured at the total hip at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

Outcome measures

Measure	Odanacatib 50 mg OW n=49 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=58 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Total Hip Using DXA	2.96 Percent change Interval 2.03 to 3.9	-0.66 Percent change Interval -1.52 to 0.2

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (trochanter aBMD) was used for analysis (PN032-Base).

aBMD was measured at the trochanter at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

Outcome measures

Measure	Odanacatib 50 mg OW n=49 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=58 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Trochanter Using DXA	5.10 Percent change Interval 3.74 to 6.45	-0.55 Percent change Interval -1.8 to 0.7

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: The per-protocol population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (s-CTx) and excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (PN032-Base).

s-CTx, a biochemical marker of bone resorption by osteoclasts reflecting collagen breakdown products, was assessed at baseline and Month 24 in an approximate 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. The log-transformed fraction from baseline in s-CTx was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=36 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=45 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base: Percent Change From Baseline in s-CTx After Log-Transformation	-55.62 Percent change Interval -62.53 to -47.44	6.62 Percent change Interval -8.51 to 24.26

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: The per-protocol population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (P1NP) and excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (PN032-Base).

P1NP is a cleavage fragment produced during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum P1NP was assessed at baseline and Month 24 in an approximate 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. The log-transformed fraction change from baseline in P1NP was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=36 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=45 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base: Percent Change From Baseline in P1NP After Log-Transformation	-33.56 Percent change Interval -42.66 to -23.01	-6.86 Percent change Interval -18.71 to 6.72

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (distal one-third radius aBMD) was used for analysis (PN032-Base).

aBMD was measured at the the distal one-third radius at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

Outcome measures

Measure	Odanacatib 50 mg OW n=49 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=55 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Distal-Third Forearm Using DXA	0.40 Percent change Interval -0.57 to 1.36	-1.27 Percent change Interval -2.18 to -0.36

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: The per-protocol population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (BSAP) and excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (PN032-Base).

BSAP is an enzyme produced by matrix-synthesizing osteoblasts during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum BSAP was assessed at baseline and Month 24 in an approximate 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. The log-transformed fraction from baseline in BSAP was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=36 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=45 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base: Percent Change From Baseline in BSAP After Log-Transformation	-12.39 Percent change Interval -19.2 to -4.99	12.64 Percent change Interval 4.53 to 21.38

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: The per-protocol population including all randomized participants who took at least one dose of study medication and having the necessary on-treatment information (u-NTx/Cr) and excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (PN032-Base).

u-NTx, a biochemical marker of bone resorption by osteoclasts reflecting collagen breakdown products, was assessed at baseline and Month 24 in an approximate 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. Urine NTx measurements (in BCE) were normalized to urine Cr concentration (i.e., u-NTx/Cr ratio) and the log-transformed fraction from baseline in u-NTx/Cr ratio was then determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.

Outcome measures

Measure	Odanacatib 50 mg OW n=36 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=45 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base: Percent Change From Baseline in u-NTx/Cr Ratio After Log-Transformation	-47.87 Percent change Interval -57.26 to -36.42	16.56 Percent change Interval -2.85 to 39.84

SECONDARY outcome

Timeframe: Baseline, Month 60

Population: The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (total hip cortical vBMD) was used for analysis (PN032-Base).

Compartment-specific effects of osteoporosis were assessed by measuring cortical vBMD at the total hip using quantitative computed tomography. The percent change from baseline at Month 60 (base study + extension study) was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

Outcome measures

Measure	Odanacatib 50 mg OW n=32 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=27 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in Cortical vBMD of the Total Hip Using Quantitative Computed Tomography	6.00 Percent change Interval 4.07 to 7.93	-2.53 Percent change Interval -4.48 to -0.59

SECONDARY outcome

Timeframe: Baseline, Month 60

Population: The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (lumbar spine aBMD) was used for analysis (PN032-Base + Extension).

aBMD was measured at the lumbar spine (L1 to L4) at baseline and Month 60 using DXA . If a vertebra was fractured at baseline or became fractured during the study, its BMD measurement was excluded from analysis. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

Outcome measures

Measure	Odanacatib 50 mg OW n=36 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=37 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Lumbar Spine Using DXA	11.80 Percent change Interval 9.86 to 13.73	0.72 Percent change Interval -1.1 to 2.54

SECONDARY outcome

Timeframe: Baseline, Month 60

Population: The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (total hip aBMD) was used for analysis (PN032-Base + Extension).

aBMD was measured at the total hip at baseline and Month 60 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

Outcome measures

Measure	Odanacatib 50 mg OW n=38 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=35 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Total Hip Using DXA	5.34 Percent change Interval 3.66 to 7.01	-5.07 Percent change Interval -6.74 to -3.41

SECONDARY outcome

Timeframe: Baseline, Month 60

Population: The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (femoral neck aBMD) was used for analysis (PN032-Base + Extension).

aBMD was measured at the femoral neck at baseline and Month 60 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

Outcome measures

Measure	Odanacatib 50 mg OW n=38 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=35 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Femoral Neck Using DXA	6.87 Percent change Interval 4.68 to 9.06	-3.11 Percent change Interval -5.26 to -0.96

SECONDARY outcome

Timeframe: Baseline, Month 60

Population: The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (trochanter aBMD) was used for analysis (PN032-Base + Extension).

aBMD was measured at the trochanter at baseline and Month 60 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

Outcome measures

Measure	Odanacatib 50 mg OW n=36 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=37 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Trochanter Using DXA	10.44 Percent change Interval 7.84 to 13.03	-4.50 Percent change Interval -7.07 to -1.94

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approximately 74 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).

The time to first TIMI-adjudicated hospitalization for unstable angina was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time to First Hospitalization for Unstable Angina Confirmed by TIMI Adjudication	0.08 Parts. with event per 100 person-years	0.10 Parts. with event per 100 person-years

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approximately 74 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).

The time to first TIMI-adjudicated cardiovascular death was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time to First Cardiovascular Death Confirmed by TIMI Adjudication	0.48 Parts. with event per 100 person-years	0.43 Parts. with event per 100 person-years

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approximately 74 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).

The time to first TIMI-adjudicated fatal definite myocardial infarction was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time to First Fatal Myocardial Infarction Confirmed by TIMI Adjudication	0.02 Parts. with event per 100 person-years	0.03 Parts. with event per 100 person-years

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approximately 74 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).

The time to first TIMI-adjudicated 3-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, or 3. non-fatal definite stroke) was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time to First 3-Point MACE Confirmed by TIMI Adjudication	1.24 Parts. with event per 100 person-years	1.06 Parts. with event per 100 person-years

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approximately 74 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).

The time to first TIMI-adjudicated all-cause death was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time to First All-Cause Death Confirmed by TIMI Adjudication	1.79 Parts. with event per 100 person-years	1.70 Parts. with event per 100 person-years

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approximately 74 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).

The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardiogram confirmation was required. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time to First New Onset ECG-Confirmed Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication	0.27 Parts. with event per 100 person-years	0.22 Parts. with event per 100 person-years

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approximately 74 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).

The time to first TIMI-adjudicated fatal or non-fatal definite myocardial infarction was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time to First Fatal or Non-Fatal Myocardial Infarction Confirmed by TIMI Adjudication	0.26 Parts. with event per 100 person-years	0.28 Parts. with event per 100 person-years

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approximately 74 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).

The time to first TIMI-adjudicated fatal or non-fatal definite stroke was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time to First Fatal or Non-Fatal Stroke Confirmed by TIMI Adjudication	0.58 Parts. with event per 100 person-years	0.42 Parts. with event per 100 person-years

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approximately 74 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).

The time to first TIMI-adjudicated any reported episode of atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were included and electrocardiogram confirmation was not required. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time to First Any Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication	0.61 Parts. with event per 100 person-years	0.50 Parts. with event per 100 person-years

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approximately 74 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).

The time to first TIMI-adjudicated fatal definite stroke was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time to First Fatal Stroke Confirmed by TIMI Adjudication	0.09 Parts. with event per 100 person-years	0.05 Parts. with event per 100 person-years

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approximately 74 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).

The time to first TIMI-adjudicated 4-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, 3. non-fatal definite stroke, or 4. hospitalization for unstable angina) was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time to First 4-Point MACE Confirmed by TIMI Adjudication	1.31 Parts. with event per 100 person-years	1.15 Parts. with event per 100 person-years

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approximately 74 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).

The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardiogram confirmation was not required. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Time to First New Onset Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication	0.51 Parts. with event per 100 person-years	0.43 Parts. with event per 100 person-years

POST_HOC outcome

Timeframe: Up to approximately 60 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).

The incidence rate of femoral shaft fracture events (including both atypical and non-atypical; of any etiology including traumatic) confirmed by adjudication was determined for the base study. Results are expressed as number of participants with an event per 100 person-years of follow-up.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Incidence Rate of Femoral Shaft Fractures Confirmed by Adjudication	0.10 Parts. with event per 100 person-years Interval 0.06 to 0.15	0.06 Parts. with event per 100 person-years Interval 0.03 to 0.1

POST_HOC outcome

Timeframe: Up to approximately 60 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).

Atypical subtrochanteric/diaphyseal femoral fractures (AFF) are an uncommon type of low-energy (eg, osteoporotic) femoral shaft fracture of unclear causation infrequently reported in osteoporotic persons treated with long-term anti-resorptive therapy (eg, bisphosphonates). All femoral (femur, femur-distal, femur-shaft) fractures in the base study were adjudicated against both ASBMR 2010 and 2013 criteria. All 5 major features (ie, location along femoral shaft, no/minimal trauma, transverse/short oblique fracture, non-comminuted, complete/incomplete fracture) were required for ASBMR 2010 AFF case definition; while 4 of 5 major features (ie, no/minimal trauma, substantially transverse orientation at cortical origin with possible oblique orientation medially, non-comminuted/minimally comminuted, complete/incomplete fracture, localized periosteal reaction of lateral cortex) with requirement for location along femoral shaft were required for ASBMR 2013 AFF case definition.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study: Incidence Rate of Atypical Femoral Shaft Fractures Confirmed by Adjudication	0.02 Parts. with event per 100 person-years Interval 0.01 to 0.05	0.00 Parts. with event per 100 person-years Interval 0.0 to 0.02

POST_HOC outcome

Timeframe: Up to approximately 74 months of observation

Population: The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).

The incidence rate of femoral shaft fracture events (including both atypical and non-atypical; of any etiology including traumatic) confirmed by adjudication was determined for the base study + first extension. Results are expressed as number of participants with an event per 100 person-years of follow-up.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Incidence Rate of Femoral Shaft Fractures Confirmed by Adjudication	0.09 Parts. with event per 100 person-years Interval 0.06 to 0.13	0.02 Parts. with event per 100 person-years Interval 0.01 to 0.05

POST_HOC outcome

Timeframe: Up to approximately 74 months of observation

Population: The All-Participants-as-Treated population, including all randomized participants who took at least one dose of study medication, was used for analysis (base study + first extension).

Atypical subtrochanteric/diaphyseal femoral fractures (AFF) are an uncommon type of low-energy (eg, osteoporotic) femoral shaft fracture of unclear causation infrequently reported in osteoporotic persons treated with long-term anti-resorptive therapy (eg, bisphosphonates). All femoral (femur, femur-distal, femur-shaft) fractures in the base study + first extension were adjudicated against both ASBMR 2010 & 2013 criteria. All 5 major features (ie, location along femoral shaft, no/minimal trauma, transverse/short oblique fracture, non-comminuted, complete/incomplete fracture) were required for ASBMR 2010 AFF case definition; while 4 of 5 major features (ie, no/minimal trauma, substantially transverse orientation at cortical origin with possible oblique orientation medially, non-comminuted/minimally comminuted, complete/incomplete fracture, localized periosteal reaction of lateral cortex) with requirement for location along femoral shaft were required for ASBMR 2013 AFF case definition.

Outcome measures

Measure	Odanacatib 50 mg OW n=8043 Participants Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Placebo n=8028 Participants Participants received blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). This was to be followed by 50 mg of open-label odanacatib weekly for up to 5 years. Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Base Study + First Extension: Incidence Rate of Atypical Femoral Shaft Fractures Confirmed by Adjudication	0.03 Parts. with event per 100 person-years Interval 0.02 to 0.06	0.00 Parts. with event per 100 person-years Interval 0.0 to 0.01

Adverse Events

Base Study + First Extension: Odanacatib 50 mg OW

Serious events: 2441 serious events

Other events: 5659 other events

Deaths: 378 deaths

Base Study + First Extension: Placebo

Serious events: 2446 serious events

Other events: 5624 other events

Deaths: 327 deaths

Second Extension: Odanacatib 50 mg OW

Serious events: 508 serious events

Other events: 311 other events

Deaths: 86 deaths

Second Extension: Odanacatib 50 mg OW (Placebo)

Serious events: 376 serious events

Other events: 209 other events

Deaths: 39 deaths

Serious adverse events

Measure	Base Study + First Extension: Odanacatib 50 mg OW n=8043 participants at risk Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Base Study + First Extension: Placebo n=8028 participants at risk Participants received blinded placebo to 10 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Second Extension: Odanacatib 50 mg OW n=3144 participants at risk Participants received 50 mg of open-label odanacatib weekly for 5 years in the second extension study after having previously received 50 mg of blinded odanacatib weekly in the base study and first extension study (5 years total). Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Second Extension: Odanacatib 50 mg OW (Placebo) n=2309 participants at risk Participants received 50 mg of open-label odanacatib weekly for 5 years in the second extension study after having previously received blinded placebo to 50 mg of odanacatib weekly in the base study and first extension study (5 years total). Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Blood and lymphatic system disorders Haemorrhagic disorder	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Anaemia	0.20% 16/8043 • Number of events 17 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.26% 21/8028 • Number of events 22 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Anaemia megaloblastic	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Anaemia vitamin B12 deficiency	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Aplastic anaemia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Coagulopathy	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Autoimmune haemolytic anaemia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Febrile neutropenia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Haemorrhagic diathesis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Hypochromic anaemia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Immune thrombocytopenic purpura	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Iron deficiency anaemia	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Lymphadenitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Lymphadenopathy	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Lymphadenopathy mediastinal	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Neutropenia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Normochromic normocytic anaemia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Pancytopenia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Polycythaemia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Pernicious anaemia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Acute left ventricular failure	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.54% 17/3144 • Number of events 17 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.39% 9/2309 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Acute myocardial infarction	0.68% 55/8043 • Number of events 57 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.69% 55/8028 • Number of events 59 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Adams-Stokes syndrome	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Angina pectoris	0.48% 39/8043 • Number of events 44 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.51% 41/8028 • Number of events 44 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Angina unstable	0.42% 34/8043 • Number of events 43 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.42% 34/8028 • Number of events 37 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.17% 4/2309 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Aortic valve disease	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Aortic valve incompetence	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Aortic valve stenosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Arrhythmia	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Arrhythmia supraventricular	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Arteriosclerosis coronary artery	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Atrial fibrillation	0.91% 73/8043 • Number of events 83 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	1.00% 80/8028 • Number of events 97 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.54% 17/3144 • Number of events 23 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.43% 10/2309 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Atrial tachycardia	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Atrioventricular block	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Atrioventricular block complete	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Atrial flutter	0.10% 8/8043 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Atrioventricular block first degree	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Atrioventricular block second degree	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Atrioventricular dissociation	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Bradyarrhythmia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Bradycardia	0.12% 10/8043 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Bundle branch block bilateral	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Bundle branch block left	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Bundle branch block right	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Acute coronary syndrome	0.12% 10/8043 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.11% 9/8028 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cardiac arrest	0.11% 9/8043 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.16% 13/8028 • Number of events 13 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cardiac disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cardiac failure	0.44% 35/8043 • Number of events 38 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.51% 41/8028 • Number of events 44 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.22% 7/3144 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.22% 5/2309 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cardiac failure acute	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cardiac failure chronic	0.09% 7/8043 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cardiac failure congestive	0.46% 37/8043 • Number of events 38 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.44% 35/8028 • Number of events 36 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.32% 10/3144 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cardiac tamponade	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cardiac valve disease	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cardiac ventricular thrombosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cardio-respiratory arrest	0.14% 11/8043 • Number of events 11 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.17% 14/8028 • Number of events 14 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cardiogenic shock	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cardiomyopathy	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cardiopulmonary failure	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cardiovascular disorder	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cardiovascular insufficiency	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Congestive cardiomyopathy	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cor pulmonale acute	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Coronary artery disease	0.39% 31/8043 • Number of events 34 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.31% 25/8028 • Number of events 28 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.22% 7/3144 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.26% 6/2309 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Coronary artery insufficiency	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Coronary artery occlusion	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Coronary artery perforation	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Coronary artery stenosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Cytotoxic cardiomyopathy	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Extrasystoles	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Heart valve incompetence	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Hypertensive cardiomyopathy	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Ischaemic cardiomyopathy	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Left ventricular failure	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Microvascular coronary artery disease	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Mitral valve disease	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Mitral valve incompetence	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Mitral valve stenosis	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Myocardial infarction	0.58% 47/8043 • Number of events 50 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.60% 48/8028 • Number of events 51 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.22% 5/2309 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Myocardial ischaemia	0.24% 19/8043 • Number of events 21 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.15% 12/8028 • Number of events 12 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.26% 6/2309 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Myocarditis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Palpitations	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Pericardial effusion	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Pericardial haemorrhage	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Postinfarction angina	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Prinzmetal angina	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Right ventricular failure	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Sinoatrial block	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Sinus bradycardia	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Pericarditis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Sinus node dysfunction	0.10% 8/8043 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.11% 9/8028 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Stress cardiomyopathy	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Supraventricular extrasystoles	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Supraventricular tachycardia	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Tachyarrhythmia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Tachycardia	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Tachycardia paroxysmal	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Tricuspid valve incompetence	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Ventricular arrhythmia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Ventricular dysfunction	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Ventricular extrasystoles	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Ventricular fibrillation	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Cardiac disorders Ventricular tachycardia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Congenital, familial and genetic disorders Atrial septal defect	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Congenital, familial and genetic disorders Congenital bronchiectasis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Congenital, familial and genetic disorders Congenital cystic kidney disease	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Congenital, familial and genetic disorders Hypertrophic cardiomyopathy	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Congenital, familial and genetic disorders Exomphalos	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Congenital, familial and genetic disorders Thyroglossal cyst	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Ear and labyrinth disorders Acute vestibular syndrome	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Ear and labyrinth disorders Deafness neurosensory	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Ear and labyrinth disorders Ear haemorrhage	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Ear and labyrinth disorders External ear disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Ear and labyrinth disorders Inner ear disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Ear and labyrinth disorders Meniere's disease	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Ear and labyrinth disorders Neurosensory hypoacusis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Ear and labyrinth disorders Otosclerosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Ear and labyrinth disorders Sudden hearing loss	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Ear and labyrinth disorders Tinnitus	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Ear and labyrinth disorders Tympanic membrane perforation	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Ear and labyrinth disorders Vertigo	0.19% 15/8043 • Number of events 16 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Ear and labyrinth disorders Vertigo positional	0.06% 5/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Endocrine disorders Adrenal haemorrhage	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Endocrine disorders Adrenal insufficiency	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Endocrine disorders Autoimmune thyroiditis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Endocrine disorders Goitre	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Endocrine disorders Hyperadrenalism	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Endocrine disorders Hyperparathyroidism	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Endocrine disorders Hyperparathyroidism primary	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Endocrine disorders Hyperthyroidism	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Endocrine disorders Hypothyroidism	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Endocrine disorders Inappropriate antidiuretic hormone secretion	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Endocrine disorders Primary hypothyroidism	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Endocrine disorders Secondary hyperthyroidism	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Endocrine disorders Thyroid cyst	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Endocrine disorders Thyroiditis subacute	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Endocrine disorders Thyroid mass	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Age-related macular degeneration	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Amaurosis fugax	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Angle closure glaucoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Blindness	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Blindness unilateral	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Cataract	1.2% 98/8043 • Number of events 131 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.98% 79/8028 • Number of events 108 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.38% 12/3144 • Number of events 16 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.39% 9/2309 • Number of events 13 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Cataract nuclear	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Chalazion	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Choroiditis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Conjunctival haemorrhage	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Corneal opacity	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Cystoid macular oedema	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Dacryostenosis acquired	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Diplopia	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Entropion	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Excessive eye blinking	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Eyelid ptosis	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Glaucoma	0.10% 8/8043 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Iritis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Keratitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Keratitis interstitial	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Keratopathy	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Lacrimal disorder	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Lens disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Macular degeneration	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Macular fibrosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Macular hole	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Maculopathy	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Myopia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Neovascular age-related macular degeneration	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Optic atrophy	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Optic ischaemic neuropathy	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Posterior capsule opacification	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Retinal artery embolism	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Retinal degeneration	0.01% 1/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Retinal detachment	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Retinal dystrophy	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Retinal haemorrhage	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Retinal vein occlusion	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Retinal vein thrombosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Retinopathy	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Trichiasis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Ulcerative keratitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Vision blurred	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Visual acuity reduced	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Visual impairment	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Vitreous haemorrhage	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Corneal scar	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Flat anterior chamber of eye	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Open angle glaucoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Abdominal adhesions	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Abdominal distension	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Abdominal hernia	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Abdominal hernia obstructive	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Abdominal pain	0.11% 9/8043 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.11% 9/8028 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Abdominal pain lower	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Abdominal pain upper	0.09% 7/8043 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Anal fissure	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Anal fistula	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Anal inflammation	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Anal stenosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Ascites	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Barrett's oesophagus	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Change of bowel habit	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Chronic gastritis	0.09% 7/8043 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Colitis	0.10% 8/8043 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Colitis ischaemic	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 7/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Colitis microscopic	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Colitis ulcerative	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Constipation	0.11% 9/8043 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.12% 10/8028 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Crohn's disease	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Dental caries	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Diarrhoea	0.15% 12/8043 • Number of events 14 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 8/8028 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Diverticular perforation	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Diverticulitis intestinal haemorrhagic	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Diverticulum	0.11% 9/8043 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.11% 9/8028 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.16% 5/3144 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Diverticulum intestinal	0.09% 7/8043 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Diverticulum intestinal haemorrhagic	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Diverticulum oesophageal	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Dolichocolon acquired	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Duodenal perforation	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Duodenal ulcer	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Duodenal ulcer perforation	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Duodenitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Dysbacteriosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Dyspepsia	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Dysphagia	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Enteritis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Enterocele	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Enterocolitis	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Enterocutaneous fistula	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Enterovesical fistula	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Erosive oesophagitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Faecal incontinence	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Faecaloma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Femoral hernia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Abdominal mass	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Anal prolapse	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Femoral hernia incarcerated	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Food poisoning	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Functional gastrointestinal disorder	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastric antral vascular ectasia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastric haemorrhage	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastric ulcer	0.06% 5/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 7/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastric ulcer haemorrhage	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastric ulcer perforation	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastritis	0.24% 19/8043 • Number of events 19 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.12% 10/8028 • Number of events 11 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastritis erosive	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastroduodenitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastrointestinal disorder	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastrointestinal angiodysplasia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastrointestinal haemorrhage	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 7/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastrointestinal inflammation	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastrointestinal motility disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastrointestinal necrosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastrointestinal obstruction	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastrointestinal ulcer haemorrhage	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastrooesophageal reflux disease	0.10% 8/8043 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.12% 10/8028 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Haematemesis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Haematochezia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Haemorrhoids	0.14% 11/8043 • Number of events 11 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.12% 10/8028 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastrointestinal ulcer	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Haemorrhoids thrombosed	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Hernial eventration	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Hiatus hernia	0.09% 7/8043 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 7/8028 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Ileus	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Ileus paralytic	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Incarcerated umbilical hernia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Inguinal hernia	0.09% 7/8043 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.14% 11/8028 • Number of events 11 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Intestinal haemorrhage	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Intestinal ischaemia	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Intestinal mass	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Intestinal obstruction	0.14% 11/8043 • Number of events 12 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.14% 11/8028 • Number of events 12 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Intestinal perforation	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Intestinal polyp	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Intestinal prolapse	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Intussusception	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Irritable bowel syndrome	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Ischiorectal hernia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Large intestine perforation	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Large intestine polyp	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.12% 10/8028 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Lumbar hernia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Mallory-Weiss syndrome	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Mechanical ileus	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Melaena	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Mesenteric artery embolism	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Mouth cyst	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Mouth ulceration	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Nausea	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Obstruction gastric	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Oesophageal achalasia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Oesophageal fistula	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Oesophageal hypomotility	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Oesophageal pain	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Oesophageal stenosis	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Oesophageal varices haemorrhage	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Oesophagitis	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Oesophagitis ulcerative	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Oral pain	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Pancreatic cyst	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Pancreatic mass	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Pancreatic pseudocyst	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Pancreatitis	0.10% 8/8043 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Pancreatitis acute	0.10% 8/8043 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Pancreatitis chronic	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Pancreatitis necrotising	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Peptic ulcer	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Peptic ulcer haemorrhage	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Peptic ulcer perforation	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Pharyngo-oesophageal diverticulum	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Rectal haemorrhage	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Rectal polyp	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Rectal prolapse	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Salivary gland calculus	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Small intestinal obstruction	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Splenic artery aneurysm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Stomach mass	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Subileus	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Thrombosis mesenteric vessel	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Toothache	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Retroperitoneal haematoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Umbilical hernia	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.12% 10/8028 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Varices oesophageal	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Volvulus	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Vomiting	0.04% 3/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Accidental death	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Adverse event	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Asthenia	0.09% 7/8043 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Capsular contracture associated with breast implant	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Chest discomfort	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Chest pain	0.27% 22/8043 • Number of events 23 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.30% 24/8028 • Number of events 25 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.17% 4/2309 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Cyst	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Death	0.82% 66/8043 • Number of events 66 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.77% 62/8028 • Number of events 62 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.45% 14/3144 • Number of events 14 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.17% 4/2309 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Device adhesion issue	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Device breakage	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Device damage	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Device dislocation	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Device malfunction	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Device material issue	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Drug intolerance	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Drug withdrawal syndrome	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Facial pain	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Fatigue	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders General physical health deterioration	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders General symptom	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Hernia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Ill-defined disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Impaired healing	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Implant site reaction	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Malaise	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Medical device complication	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Multi-organ disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Multi-organ failure	0.12% 10/8043 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Nodule	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Non-cardiac chest pain	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.17% 4/2309 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Oedema	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Oedema peripheral	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Oral administration complication	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Pain	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Peripheral swelling	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Pyrexia	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 7/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Soft tissue inflammation	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Strangulated hernia	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Sudden death	0.19% 15/8043 • Number of events 15 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Systemic inflammatory response syndrome	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
General disorders Organ failure	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Bile duct obstruction	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Bile duct stenosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Bile duct stone	0.11% 9/8043 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Biliary colic	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Biliary fistula	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Cholangitis	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Cholangitis acute	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Cholecystitis	0.25% 20/8043 • Number of events 20 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.19% 15/8028 • Number of events 15 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Cholecystitis acute	0.09% 7/8043 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.19% 15/8028 • Number of events 15 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Cholecystitis chronic	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Cholelithiasis	0.42% 34/8043 • Number of events 34 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.42% 34/8028 • Number of events 38 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.22% 7/3144 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Chronic hepatitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Gallbladder disorder	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Gallbladder polyp	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Hepatic cirrhosis	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Hepatic cyst	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Hepatic failure	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Hepatic steatosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Hepatitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Hepatitis cholestatic	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Hepatorenal failure	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Jaundice	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Liver disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Non-alcoholic steatohepatitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Post cholecystectomy syndrome	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Hydrocholecystis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Perforation bile duct	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Hepatobiliary disorders Portal vein thrombosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Immune system disorders Anaphylactic reaction	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Immune system disorders Anaphylactic shock	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Immune system disorders Drug hypersensitivity	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Immune system disorders Hypersensitivity	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Immune system disorders Sarcoidosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Abdominal abscess	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Abdominal sepsis	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Abdominal wall abscess	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Abscess	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Abscess limb	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Abscess neck	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Acute sinusitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Amoebic colitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Appendicitis	0.22% 18/8043 • Number of events 18 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.15% 12/8028 • Number of events 12 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.19% 6/3144 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Appendicitis perforated	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Arthritis bacterial	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Arthritis infective	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Bacteraemia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Beta haemolytic streptococcal infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Bronchiolitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Bronchitis	0.19% 15/8043 • Number of events 15 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.17% 14/8028 • Number of events 15 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Bronchopneumonia	0.22% 18/8043 • Number of events 19 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.21% 17/8028 • Number of events 18 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Burn infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Campylobacter infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Carbuncle	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Catheter site infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Cellulitis	0.19% 15/8043 • Number of events 17 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.20% 16/8028 • Number of events 20 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Central nervous system viral infection	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Chlamydial infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Cholecystitis infective	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Chronic sinusitis	0.01% 1/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Clostridium difficile colitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Clostridium difficile infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Cutaneous tuberculosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Cystitis	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 8/8028 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Cytomegalovirus gastrointestinal infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Cytomegalovirus infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Dacryocystitis	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Dengue fever	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Dental fistula	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Device related infection	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Device related sepsis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Diabetic gangrene	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Diarrhoea infectious	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Diverticulitis	0.31% 25/8043 • Number of events 27 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.25% 20/8028 • Number of events 22 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.17% 4/2309 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Dysentery	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Endophthalmitis	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Enteritis infectious	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Enterobacter pneumonia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Erysipelas	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Erythema migrans	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Escherichia urinary tract infection	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Gallbladder empyema	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Gangrene	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Gastritis viral	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Gastroenteritis	0.42% 34/8043 • Number of events 34 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.32% 26/8028 • Number of events 27 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Gastroenteritis bacterial	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Gastroenteritis clostridial	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Gastroenteritis rotavirus	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Gastroenteritis salmonella	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Gastroenteritis viral	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Gastrointestinal infection	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Gastrointestinal viral infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Endocarditis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Endometritis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Epstein-Barr virus infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Extradural abscess	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Gastroenteritis norovirus	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Diverticulitis intestinal haemorrhagic	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Genital candidiasis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Graft infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Groin abscess	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Haematoma infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Helicobacter gastritis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Helicobacter infection	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Hepatitis A	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Hepatitis E	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Herpes simplex encephalitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Herpes zoster	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Herpes zoster infection neurological	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Incision site infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Implant site infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Infected bites	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Infected dermal cyst	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Infected varicose vein	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Infective exacerbation of bronchiectasis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 7/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Influenza	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Intervertebral discitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Intestinal fistula infection	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Keratitis bacterial	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Klebsiella bacteraemia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Labyrinthitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Laryngitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Liver abscess	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Lobar pneumonia	0.14% 11/8043 • Number of events 11 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.15% 12/8028 • Number of events 12 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Localised infection	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Lower respiratory tract infection	0.16% 13/8043 • Number of events 13 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.11% 9/8028 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.16% 5/3144 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Lower respiratory tract infection bacterial	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Lung infection	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Lyme disease	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Malaria	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Mediastinitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Meningitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Meningitis bacterial	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Neurosyphilis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Neutropenic sepsis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Oesophageal candidiasis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Oral candidiasis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Osteomyelitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Otitis media	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pancreatic abscess	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Parotitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pelvic sepsis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Periorbital cellulitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Peritonitis	0.09% 7/8043 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Peritonsillar abscess	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Peritonsillitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pharyngitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pharyngotonsillitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pneumonia	1.5% 117/8043 • Number of events 134 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	1.4% 116/8028 • Number of events 121 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.99% 31/3144 • Number of events 32 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.82% 19/2309 • Number of events 19 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pneumonia bacterial	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pneumonia mycoplasmal	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pneumonia necrotising	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pneumonia pneumococcal	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pneumonia viral	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Post procedural infection	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Postoperative wound infection	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pseudomembranous colitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pseudomonal bacteraemia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pulmonary echinococciasis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pulmonary sepsis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pulmonary tuberculosis	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pyelocystitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pyelonephritis	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 7/8028 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pyelonephritis acute	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pyelonephritis chronic	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pyometra	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Pyonephrosis	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Renal abscess	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Respiratory syncytial virus infection	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Respiratory tract infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Salmonellosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Sepsis	0.29% 23/8043 • Number of events 24 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.22% 18/8028 • Number of events 19 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.22% 5/2309 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Septic shock	0.15% 12/8043 • Number of events 12 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 7/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.19% 6/3144 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Sialoadenitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Sinobronchitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Sinusitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Skin infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Staphylococcal bacteraemia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Staphylococcal sepsis	0.01% 1/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Staphylococcal skin infection	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Stoma site abscess	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Subcutaneous abscess	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Subdiaphragmatic abscess	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Tick-borne fever	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Tonsillitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Tooth infection	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Tracheitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cerebral thrombosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Upper respiratory tract infection	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Urinary tract infection	0.67% 54/8043 • Number of events 58 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.61% 49/8028 • Number of events 59 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.51% 16/3144 • Number of events 16 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.39% 9/2309 • Number of events 11 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Urinary tract infection bacterial	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Urinary tract infection pseudomonal	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Urosepsis	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Vestibular neuronitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Viral infection	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Viral labyrinthitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Viral upper respiratory tract infection	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Wound infection	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 7/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Wound infection staphylococcal	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Wound sepsis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Abdominal wound dehiscence	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Acetabulum fracture	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Anastomotic leak	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Animal bite	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Ankle fracture	0.16% 13/8043 • Number of events 15 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.24% 19/8028 • Number of events 23 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Aortic injury	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Arterial injury	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Arterial restenosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Arthropod bite	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Atypical femur fracture	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Back injury	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Bladder injury	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Bone contusion	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Bone fissure	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Cardiac valve rupture	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Cervical vertebral fracture	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Chillblains	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Clavicle fracture	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 8/8028 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Comminuted fracture	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Compression fracture	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Concussion	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 8/8028 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Contusion	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.19% 15/8028 • Number of events 18 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Craniocerebral injury	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Excoriation	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Drug dispensing error	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Extradural haematoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Face injury	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Facial bones fracture	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Fall	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Femoral neck fracture	0.36% 29/8043 • Number of events 29 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.77% 62/8028 • Number of events 64 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.39% 9/2309 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Femur fracture	0.55% 44/8043 • Number of events 49 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.50% 40/8028 • Number of events 41 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.25% 8/3144 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.17% 4/2309 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Fibula fracture	0.14% 11/8043 • Number of events 11 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.12% 10/8028 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Foot fracture	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.11% 9/8028 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Forearm fracture	0.01% 1/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Fracture displacement	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Fractured ischium	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Fractured sacrum	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Gun shot wound	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Hand fracture	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Head injury	0.10% 8/8043 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.16% 13/8028 • Number of events 13 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Heat exhaustion	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Heat illness	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Heat stroke	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Hip fracture	0.68% 55/8043 • Number of events 56 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	1.3% 104/8028 • Number of events 105 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.19% 6/3144 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.26% 6/2309 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Humerus fracture	0.35% 28/8043 • Number of events 29 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.64% 51/8028 • Number of events 51 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.30% 7/2309 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Incisional hernia	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Injury	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Jaw fracture	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Joint dislocation	0.07% 6/8043 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Joint injury	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Laceration	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Ligament rupture	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Ligament sprain	0.02% 2/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Limb crushing injury	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Limb injury	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Limb traumatic amputation	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Lower limb fracture	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.16% 13/8043 • Number of events 17 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.31% 25/8028 • Number of events 27 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.19% 6/3144 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Meniscus injury	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Mouth injury	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Multiple injuries	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Muscle injury	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Muscle rupture	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Muscle strain	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Nerve root injury lumbar	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Patella fracture	0.10% 8/8043 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.14% 11/8028 • Number of events 11 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.16% 5/3144 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Pelvic fracture	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Perineal injury	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Post procedural complication	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Post procedural discomfort	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Post procedural fistula	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Post procedural haematoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Post procedural haemorrhage	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Post procedural inflammation	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Post procedural swelling	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Post procedural oedema	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Post-traumatic neck syndrome	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Postoperative adhesion	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Postoperative hernia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Postoperative ileus	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Postoperative respiratory failure	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Procedural complication	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Procedural haemorrhage	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Procedural nausea	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Procedural pain	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Pubis fracture	0.14% 11/8043 • Number of events 12 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 7/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Pulmonary contusion	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Radius fracture	0.82% 66/8043 • Number of events 68 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.96% 77/8028 • Number of events 79 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.26% 6/2309 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Rib fracture	0.09% 7/8043 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.12% 10/8028 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Road traffic accident	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Scapula fracture	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Scar	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Skin abrasion	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Skin injury	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Skin wound	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Skull fracture	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Skull fractured base	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Soft tissue injury	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Spinal column injury	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Spinal compression fracture	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Spinal cord injury cervical	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Spinal fracture	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Splenic rupture	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Sternal fracture	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Sternal injury	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Subcutaneous haematoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Subarachnoid haemorrhage	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Subdural haematoma	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Subdural haemorrhage	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Synovial rupture	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Tendon injury	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Tendon rupture	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Thermal burn	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.15% 12/8043 • Number of events 13 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.29% 23/8028 • Number of events 28 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Tibia fracture	0.16% 13/8043 • Number of events 13 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.27% 22/8028 • Number of events 22 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Toxicity to various agents	0.02% 2/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Traumatic haemorrhage	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Traumatic haemothorax	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Traumatic intracranial haemorrhage	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Traumatic shock	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Ulna fracture	0.19% 15/8043 • Number of events 17 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.35% 28/8028 • Number of events 28 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Ulnar nerve injury	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Upper limb fracture	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Vascular injury	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Vascular pseudoaneurysm	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Wound	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Wound dehiscence	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Wound haemorrhage	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Wrist fracture	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Alanine aminotransferase increased	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Aspartate aminotransferase increased	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Blood calcium decreased	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Blood cortisol increased	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Blood creatinine increased	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Blood parathyroid hormone increased	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Blood pressure increased	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Blood urea increased	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Coagulation time prolonged	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Electrocardiogram QT prolonged	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Electrocardiogram abnormal	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Grip strength decreased	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Haemoglobin decreased	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Heart rate irregular	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations International normalised ratio decreased	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Investigation	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Myocardial necrosis marker increased	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Occult blood positive	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Residual urine volume increased	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Investigations Weight decreased	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Cachexia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Decreased appetite	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Dehydration	0.16% 13/8043 • Number of events 13 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 7/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Diabetes mellitus	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.12% 10/8028 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.10% 8/8043 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.11% 9/8028 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Diabetic ketoacidosis	0.05% 4/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Diabetic metabolic decompensation	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Electrolyte imbalance	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Gout	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Hyperglycaemia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Hyperkalaemia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Hyperosmolar state	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Hypoglycaemia	0.10% 8/8043 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Hypokalaemia	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Hyponatraemia	0.10% 8/8043 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.17% 14/8028 • Number of events 15 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Hypophagia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Hypovolaemia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Ketoacidosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Malnutrition	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Metabolic acidosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Metabolic disorder	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Type 1 diabetes mellitus	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Arthralgia	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Arthritis	0.15% 12/8043 • Number of events 13 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 8/8028 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Arthritis reactive	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Atlantoaxial instability	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Axillary mass	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Back pain	0.25% 20/8043 • Number of events 20 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.27% 22/8028 • Number of events 22 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Bone loss	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Bone pain	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Bursitis	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Chondrocalcinosis pyrophosphate	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Chondropathy	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Connective tissue disorder	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Costochondritis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Dupuytren's contracture	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Eosinophilic fasciitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Facet joint syndrome	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Foot deformity	0.15% 12/8043 • Number of events 14 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.12% 10/8028 • Number of events 11 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Fracture delayed union	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Fracture malunion	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Fracture pain	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Haemarthrosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.15% 12/8043 • Number of events 12 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.12% 10/8028 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Intervertebral disc space narrowing	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Jaw cyst	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Joint adhesion	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Joint contracture	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Joint effusion	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Joint range of motion decreased	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Joint stiffness	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Joint swelling	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Knee deformity	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.11% 9/8043 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Mobility decreased	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Monarthritis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Morphoea	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Muscle spasms	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Muscular weakness	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.09% 7/8043 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Myalgia	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Nodal osteoarthritis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Osteoarthritis	1.7% 135/8043 • Number of events 154 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	1.4% 115/8028 • Number of events 132 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.38% 12/3144 • Number of events 12 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.52% 12/2309 • Number of events 13 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Osteochondritis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Osteochondrosis	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Osteonecrosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Osteosclerosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Pain in extremity	0.11% 9/8043 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Periarthritis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Periostitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Plantar fasciitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Polymyalgia rheumatica	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 7/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.22% 18/8043 • Number of events 18 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.14% 11/8028 • Number of events 12 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Scleroderma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Scoliosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Sjogren's syndrome	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Soft tissue necrosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.19% 15/8043 • Number of events 15 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.21% 17/8028 • Number of events 17 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 7/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Spinal pain	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Spondylitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Spondyloarthropathy	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Synovial cyst	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Synovitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Tendonitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Tenosynovitis stenosans	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Trigger finger	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Ulnocarpal abutment syndrome	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Abdominal neoplasm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute leukaemia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma gastric	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of appendix	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.12% 10/8043 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 7/8028 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of the cervix	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Anal cancer	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Angiosarcoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Astrocytoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.98% 79/8043 • Number of events 93 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.88% 71/8028 • Number of events 87 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.29% 9/3144 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.35% 8/2309 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign breast neoplasm	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign gastric neoplasm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign lung neoplasm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign muscle neoplasm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of bladder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of thyroid gland	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of skin	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign salivary gland neoplasm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign vulval neoplasm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bile duct cancer	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder neoplasm	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone cancer	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone neoplasm	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Borderline mucinous tumour of ovary	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain cancer metastatic	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.41% 33/8043 • Number of events 33 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.40% 32/8028 • Number of events 32 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.39% 9/2309 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer recurrent	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer in situ	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer stage III	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast neoplasm	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchial carcinoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchioloalveolar carcinoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoid tumour of the stomach	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoma in situ of skin	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cardiac myxoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cerebellar tumour	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cerebellopontine angle tumour	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix cancer metastatic	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma recurrent	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma stage II	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chondroma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Choroid melanoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Clear cell endometrial carcinoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.29% 23/8043 • Number of events 23 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.21% 17/8028 • Number of events 17 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer metastatic	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon neoplasm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer recurrent	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma stage IV	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ductal adenocarcinoma of pancreas	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Duodenal neoplasm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Dysplastic naevus	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial adenocarcinoma	0.05% 4/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Essential thrombocythaemia	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fallopian tube cancer	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Female reproductive neoplasm	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibroadenoma of breast	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibroma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibromatosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Follicle centre lymphoma, follicular grade I, II, III stage II	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gallbladder adenocarcinoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gallbladder cancer	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer stage IV	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric neoplasm	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal carcinoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal neoplasm	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal stromal tumour	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal tract adenoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gingival cancer	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma multiforme	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glomus tumour	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of bone	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic cancer	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Inflammatory carcinoma of the breast	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal papilloma of breast	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraocular melanoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive breast carcinoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.09% 7/8043 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive lobular breast carcinoma	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Kaposi's sarcoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Keratoacanthoma	0.04% 3/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal squamous cell carcinoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leiomyoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leiomyosarcoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lentigo maligna	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lip and/or oral cavity cancer	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lip squamous cell carcinoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Liposarcoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lobular breast carcinoma in situ	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.10% 8/8043 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma stage I	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma stage IV	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung carcinoma cell type unspecified stage IV	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.16% 13/8043 • Number of events 13 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.29% 23/8028 • Number of events 24 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphangioma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoproliferative disorder	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma in situ	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm of ampulla of Vater	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm of eyelid	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm of renal pelvis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm of unknown primary site	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant peritoneal neoplasm	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mantle cell lymphoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Medullary thyroid cancer	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanoma recurrent	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mesothelioma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mesothelioma malignant	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metaplastic breast carcinoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lung	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lymph nodes	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to peritoneum	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to pleura	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to skin	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastasis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic bronchial carcinoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic gastric cancer	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic malignant melanoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic salivary gland cancer	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic uterine cancer	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mixed adenoneuroendocrine carcinoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mucinous breast carcinoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mycosis fungoides	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome transformation	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myeloproliferative disorder	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Nasal cavity cancer	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Nasal neoplasm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Nasopharyngeal cancer	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine carcinoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine carcinoma metastatic	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine tumour	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer metastatic	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer stage IV	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal adenocarcinoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal squamous cell carcinoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oligodendroglioma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oropharyngeal cancer	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Osteoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Osteosarcoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian adenoma	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.09% 7/8043 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer metastatic	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian epithelial cancer stage I	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian neoplasm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.16% 13/8043 • Number of events 13 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.11% 9/8028 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma stage IV	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic neoplasm	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary serous endometrial carcinoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papilloma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Parathyroid tumour benign	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pelvic neoplasm	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Peritoneal mesothelioma malignant	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pharyngeal cancer	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasmacytoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pleural neoplasm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Primary myelofibrosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pyogenic granuloma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenocarcinoma	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenoma	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal neoplasm	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectosigmoid cancer	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Refractory anaemia with an excess of blasts	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Refractory cytopenia with unilineage dysplasia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma stage II	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal neoplasm	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal oncocytoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Retroperitoneal cancer	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Salivary gland cancer	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Sarcoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Schwannoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin cancer	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer limited stage	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Soft tissue neoplasm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Spinal cord neoplasm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Splenic marginal zone lymphoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.17% 14/8043 • Number of events 14 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.15% 12/8028 • Number of events 12 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.22% 18/8043 • Number of events 20 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.12% 10/8028 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the cervix	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the oral cavity	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the tongue	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Superficial spreading melanoma stage unspecified	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) T-cell lymphoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thymoma malignant	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid adenoma	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer metastatic	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid neoplasm	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tongue neoplasm malignant stage unspecified	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tonsil cancer	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell cancer of the renal pelvis and ureter	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ureteric cancer	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.09% 7/8043 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine neoplasm	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Vulval cancer	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Vulval cancer stage 0	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Altered state of consciousness	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Amnesia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Amyotrophic lateral sclerosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Apallic syndrome	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Aphasia	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Ataxia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Balance disorder	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Basal ganglia haemorrhage	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Basal ganglia infarction	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Brain injury	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Brain oedema	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Brain stem infarction	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Brain stem stroke	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Carotid arteriosclerosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Carotid artery aneurysm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Carotid artery disease	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Carotid artery occlusion	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Carotid artery stenosis	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Carotid artery thrombosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Carotid sinus syndrome	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Carpal tunnel syndrome	0.11% 9/8043 • Number of events 11 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cerebellar infarction	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cerebellar ischaemia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cerebral arteriosclerosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cerebral artery embolism	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cerebral circulatory failure	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cerebral haematoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cerebral haemorrhage	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.11% 9/8028 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cerebral infarction	0.39% 31/8043 • Number of events 32 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.22% 18/8028 • Number of events 18 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.22% 5/2309 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cerebral ischaemia	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 8/8028 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cerebral venous thrombosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cerebrovascular accident	0.85% 68/8043 • Number of events 68 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.52% 42/8028 • Number of events 43 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.25% 8/3144 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.17% 4/2309 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cerebrovascular disorder	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cerebrovascular insufficiency	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cervical myelopathy	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cervical radiculopathy	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cognitive disorder	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Coma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Complex partial seizures	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Cranial nerve disorder	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Dementia	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Dementia Alzheimer's type	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Depressed level of consciousness	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Diabetic neuropathy	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Dizziness	0.10% 8/8043 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 7/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Dysarthria	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Dyslalia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Embolic cerebral infarction	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Encephalopathy	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Epilepsy	0.07% 6/8043 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Frontotemporal dementia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Generalised tonic-clonic seizure	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Guillain-Barre syndrome	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Haemorrhage intracranial	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Haemorrhagic stroke	0.12% 10/8043 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Headache	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Hemiparesis	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Hemiplegia	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Hepatic encephalopathy	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Hydrocephalus	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Hypertensive encephalopathy	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Hypertonia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Hypoglycaemic coma	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Hypoglycaemic unconsciousness	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Hypotonia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders IVth nerve paralysis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders IIIrd nerve paralysis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Intracranial aneurysm	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Intracranial haematoma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Intracranial venous sinus thrombosis	0.01% 1/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Ischaemic cerebral infarction	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Ischaemic neuropathy	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Ischaemic stroke	0.48% 39/8043 • Number of events 40 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.50% 40/8028 • Number of events 41 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.67% 21/3144 • Number of events 22 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.30% 7/2309 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Lacunar infarction	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 8/8028 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Loss of consciousness	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 8/8028 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Lumbar radiculopathy	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Memory impairment	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Meningorrhagia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Metabolic encephalopathy	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Migraine	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Morton's neuralgia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Motor neurone disease	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Nerve root compression	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Myasthenia gravis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Nerve compression	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Neuritis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Neuropathy peripheral	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Normal pressure hydrocephalus	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Paraesthesia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Paraparesis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Parkinson's disease	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Parkinsonism	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Partial seizures	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Peripheral nerve lesion	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Peripheral sensorimotor neuropathy	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Polyneuropathy	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Post herpetic neuralgia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Presyncope	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Radicular syndrome	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Radiculopathy	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Ruptured cerebral aneurysm	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Sciatica	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Sedation	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Seizure	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Senile dementia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Sensory disturbance	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Slow speech	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Spinal cord compression	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Spinal cord haemorrhage	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Status epilepticus	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Subarachnoid haemorrhage	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Syncope	0.39% 31/8043 • Number of events 33 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.25% 20/8028 • Number of events 20 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.17% 4/2309 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Thalamus haemorrhage	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Thrombotic stroke	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Transient global amnesia	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Transient ischaemic attack	0.39% 31/8043 • Number of events 33 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.44% 35/8028 • Number of events 38 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Trigeminal neuralgia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders VIIth nerve paralysis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Vascular dementia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Vascular encephalopathy	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Vertebral artery stenosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Vertebrobasilar insufficiency	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders White matter lesion	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Alcohol abuse	0.01% 1/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Alcohol withdrawal syndrome	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Anxiety	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Anxiety disorder	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Anxiety disorder due to a general medical condition	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Bipolar disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Completed suicide	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Compulsive hoarding	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Confusional state	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Delirium	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Depression	0.12% 10/8043 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.12% 10/8028 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Dysphemia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Dysthymic disorder	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Major depression	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Mental disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Mood disorder due to a general medical condition	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Panic attack	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Psychogenic pain disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Psychogenic seizure	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Psychotic disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Psychiatric disorders Suicide attempt	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Acute kidney injury	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Acute prerenal failure	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Azotaemia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Bladder cyst	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Bladder diverticulum	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Bladder irritation	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Bladder perforation	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Bladder prolapse	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Calculus bladder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Calculus ureteric	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Calculus urethral	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Calculus urinary	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Chronic kidney disease	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Cystitis haemorrhagic	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Glomerulonephritis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Glomerulonephritis membranous	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Glomerulonephritis rapidly progressive	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Haematuria	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Hydronephrosis	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Hypertonic bladder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Nephrotic syndrome	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Nephrolithiasis	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.12% 10/8028 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Oliguria	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Pollakiuria	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Renal artery stenosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Renal colic	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Renal failure	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Renal impairment	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Renal mass	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Renal tubular disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Scleroderma renal crisis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Stress urinary incontinence	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Tubulointerstitial nephritis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Ureteric stenosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Urethral caruncle	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Urethral polyp	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Urethral stenosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Urinary bladder polyp	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Urinary incontinence	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Renal and urinary disorders Urinary retention	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Adnexal torsion	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Adnexa uteri mass	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Anisomastia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Breast mass	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Cervical dysplasia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Cervical polyp	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Colpocele	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Cystocele	0.09% 7/8043 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Dysfunctional uterine bleeding	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Endometrial hyperplasia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Genital labial adhesions	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Hydrometra	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Metrorrhagia	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Ovarian cyst	0.15% 12/8043 • Number of events 12 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Pelvic floor muscle weakness	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Pelvic pain	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Pelvic prolapse	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Postmenopausal haemorrhage	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Rectocele	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Uterine polyp	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Vaginal polyp	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Uterine prolapse	0.17% 14/8043 • Number of events 15 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.16% 13/8028 • Number of events 14 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Vaginal fistula	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Vaginal haemorrhage	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Vaginal prolapse	0.09% 7/8043 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.12% 10/8028 • Number of events 10 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Vulval leukoplakia	0.02% 2/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Vulvar dysplasia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Vulvovaginal pruritus	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.04% 3/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.11% 9/8028 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Asthma	0.12% 10/8043 • Number of events 11 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.21% 17/8028 • Number of events 20 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Asthmatic crisis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.42% 34/8043 • Number of events 43 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.45% 36/8028 • Number of events 44 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.29% 9/3144 • Number of events 11 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.22% 5/2309 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Chronic respiratory disease	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Emphysema	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Eosinophilic pneumonia chronic	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Epiglottic cyst	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Epistaxis	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Haemothorax	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Hydrothorax	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.01% 1/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Laryngeal dysplasia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Laryngeal granuloma	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Laryngeal polyp	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Lung consolidation	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Lung disorder	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Mediastinal cyst	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Nasal polyps	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Oesophagobronchial fistula	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Pharyngeal pouch	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Pickwickian syndrome	0.01% 1/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.16% 13/8043 • Number of events 14 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 8/8028 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Pleurisy	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.07% 6/8043 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Pulmonary arteriopathy	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.35% 28/8043 • Number of events 29 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.35% 28/8028 • Number of events 30 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.22% 7/3144 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.10% 8/8043 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Pulmonary ossification	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Pulmonary thrombosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.04% 3/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.16% 13/8043 • Number of events 14 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.11% 9/8028 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Respiratory tract inflammation	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Sinus polyp	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Sinus polyp degeneration	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Throat irritation	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Tracheal stenosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Vocal cord disorder	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Vocal cord polyp	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Actinic keratosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Acute generalised exanthematous pustulosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Angioedema	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Atrophoderma of Pasini and Pierini	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Blister	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Dermal cyst	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Dermatitis allergic	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Dermatitis atopic	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Dermatomyositis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Diabetic foot	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Eczema	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Eczema asteatotic	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Erythema nodosum	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Hand dermatitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Henoch-Schonlein purpura	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Hyperkeratosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Hypersensitivity vasculitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Ingrowing nail	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Lentigo	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Leukoplakia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Lichen sclerosus	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Neurodermatitis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Pemphigoid	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Pemphigus	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Pruritus generalised	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Psoriasis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Pyoderma gangrenosum	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Rash	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Rash erythematous	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Rash generalised	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Skin ulcer	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.07% 6/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Skin wrinkling	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Skin and subcutaneous tissue disorders Urticaria	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Social circumstances Immobile	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Accelerated hypertension	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Aortic aneurysm	0.10% 8/8043 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Aortic aneurysm rupture	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Aortic arteriosclerosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Aortic disorder	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Aortic dissection	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Aortic stenosis	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Arterial disorder	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Arterial stenosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Arteriosclerosis	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Bleeding varicose vein	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Blood pressure fluctuation	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Circulatory collapse	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Deep vein thrombosis	0.21% 17/8043 • Number of events 19 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.11% 9/8028 • Number of events 9 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 3/2309 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Distributive shock	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Essential hypertension	0.01% 1/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Iliac artery embolism	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Extremity necrosis	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Femoral artery occlusion	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Haematoma	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Hot flush	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Hypertension	0.39% 31/8043 • Number of events 34 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.46% 37/8028 • Number of events 39 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.17% 4/2309 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Hypertensive crisis	0.12% 10/8043 • Number of events 12 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.25% 20/8028 • Number of events 21 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.13% 4/3144 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Hypertensive emergency	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Hypotension	0.09% 7/8043 • Number of events 7 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.09% 2/2309 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Hypovolaemic shock	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Iliac artery occlusion	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Infarction	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Intermittent claudication	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Malignant hypertension	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Necrosis ischaemic	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Orthostatic hypotension	0.06% 5/8043 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Peripheral arterial occlusive disease	0.09% 7/8043 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 5/8028 • Number of events 6 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.10% 3/3144 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Peripheral artery stenosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Peripheral artery thrombosis	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Peripheral circulatory failure	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Peripheral ischaemia	0.05% 4/8043 • Number of events 4 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.06% 2/3144 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Peripheral vascular disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Peripheral venous disease	0.04% 3/8043 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Phlebitis	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Shock haemorrhagic	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Subgaleal haematoma	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Temporal arteritis	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Thrombophlebitis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.05% 4/8028 • Number of events 5 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Thrombophlebitis superficial	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Thrombosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Varicose ulceration	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Varicose vein	0.10% 8/8043 • Number of events 8 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 3/8028 • Number of events 3 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Vasculitis	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Vena cava thrombosis	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Venous thrombosis	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.02% 2/8028 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Venous thrombosis limb	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Ciliary body disorder	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Gastric polyps	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Vaginal abscess	0.01% 1/8043 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.02% 2/8043 • Number of events 2 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Urethral cancer	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Cervical leukoplakia	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Reproductive system and breast disorders Genital prolapse	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.01% 1/8028 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Bronchitis bacterial	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.04% 1/2309 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the vagina	0.00% 0/8043 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/8028 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.03% 1/3144 • Number of events 1 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).

Other adverse events

Measure	Base Study + First Extension: Odanacatib 50 mg OW n=8043 participants at risk Participants received 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Base Study + First Extension: Placebo n=8028 participants at risk Participants received blinded placebo to 10 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Second Extension: Odanacatib 50 mg OW n=3144 participants at risk Participants received 50 mg of open-label odanacatib weekly for 5 years in the second extension study after having previously received 50 mg of blinded odanacatib weekly in the base study and first extension study (5 years total). Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.	Second Extension: Odanacatib 50 mg OW (Placebo) n=2309 participants at risk Participants received 50 mg of open-label odanacatib weekly for 5 years in the second extension study after having previously received blinded placebo to 50 mg of odanacatib weekly in the base study and first extension study (5 years total). Participants also received Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) was approximately 1200 mg.
Blood and lymphatic system disorders Anaemia	5.9% 477/8043 • Number of events 552 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	6.2% 500/8028 • Number of events 583 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Eye disorders Cataract	6.1% 488/8043 • Number of events 638 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	6.1% 492/8028 • Number of events 652 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Constipation	6.1% 492/8043 • Number of events 547 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	6.3% 504/8028 • Number of events 552 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Gastrointestinal disorders Diarrhoea	7.3% 589/8043 • Number of events 726 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	6.3% 504/8028 • Number of events 608 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Bronchitis	5.6% 450/8043 • Number of events 591 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	5.7% 459/8028 • Number of events 611 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Influenza	6.2% 495/8043 • Number of events 610 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	5.5% 443/8028 • Number of events 564 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Nasopharyngitis	11.9% 957/8043 • Number of events 1396 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	11.7% 938/8028 • Number of events 1365 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Upper respiratory tract infection	8.0% 644/8043 • Number of events 962 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	7.4% 596/8028 • Number of events 913 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Infections and infestations Urinary tract infection	21.4% 1724/8043 • Number of events 2911 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	21.2% 1699/8028 • Number of events 2821 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	9.9% 311/3144 • Number of events 393 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	9.1% 209/2309 • Number of events 271 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Accidental overdose	5.9% 476/8043 • Number of events 761 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	6.2% 499/8028 • Number of events 736 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Injury, poisoning and procedural complications Contusion	4.8% 386/8043 • Number of events 500 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	5.3% 422/8028 • Number of events 568 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Arthralgia	15.2% 1221/8043 • Number of events 1588 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	14.3% 1151/8028 • Number of events 1533 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Back pain	14.8% 1194/8043 • Number of events 1473 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	14.2% 1136/8028 • Number of events 1394 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.4% 518/8043 • Number of events 589 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	5.7% 461/8028 • Number of events 537 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Osteoarthritis	9.8% 785/8043 • Number of events 980 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	9.2% 741/8028 • Number of events 910 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Musculoskeletal and connective tissue disorders Pain in extremity	9.3% 751/8043 • Number of events 923 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	8.4% 671/8028 • Number of events 797 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Nervous system disorders Dizziness	6.1% 492/8043 • Number of events 574 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	6.0% 483/8028 • Number of events 565 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Respiratory, thoracic and mediastinal disorders Cough	5.9% 471/8043 • Number of events 553 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	5.8% 466/8028 • Number of events 544 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
Vascular disorders Hypertension	13.7% 1104/8043 • Number of events 1263 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	13.5% 1084/8028 • Number of events 1278 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/3144 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).	0.00% 0/2309 • Base Study + First Extension treatment groups: Up to approximately 74 months of observation Second Extension treatment groups: Up to approximately 34 months of observation The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).

Additional Information

Senior Vice President, Global Clinical Development,

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication guidelines.
• Publication restrictions are in place

Restriction type: OTHER