Trial Outcomes & Findings for Abiraterone Acetate in Asymptomatic or Mildly Symptomatic Patients With Metastatic Castration-Resistant Prostate Cancer (NCT NCT00887198)

NCT ID: NCT00887198

Last Updated: 2025-02-04

Results Overview

Overall survival is defined as the time from randomization to date of death from any cause.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1088 participants
• Primary outcome timeframe: From randomization (Day 1) up to end of study (Month 60)
• Results posted on: 2025-02-04

Participant Flow

Participant milestones

Measure	Abiraterone Acetate + Prednisone (AAP) Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4\*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo to AA Participants who were originally assigned to placebo were later on switched to 1,000 milligram (mg) abiraterone acetate tablet (as 4\*250 mg tablets) along with prednisone 5 mg tablet.
Randomized Period STARTED	546	542	0
Randomized Period Treated	542	540	0
Randomized Period COMPLETED	0	0	0
Randomized Period NOT COMPLETED	546	542	0
Cross Over (Placebo to AA) STARTED	0	0	93
Cross Over (Placebo to AA) COMPLETED	0	0	0
Cross Over (Placebo to AA) NOT COMPLETED	0	0	93

Reasons for withdrawal

Measure	Abiraterone Acetate + Prednisone (AAP) Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4\*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo to AA Participants who were originally assigned to placebo were later on switched to 1,000 milligram (mg) abiraterone acetate tablet (as 4\*250 mg tablets) along with prednisone 5 mg tablet.
Randomized Period Ongoing	42	0	0
Randomized Period Adverse Event	50	33	0
Randomized Period Lost to Follow-up	1	0	0
Randomized Period Cross-over to AA (under amendment 3)	0	51	0
Randomized Period Withdrawal by Subject	41	56	0
Randomized Period Progressive disease	366	370	0
Randomized Period Other	42	30	0
Randomized Period Randomized, Not treated	4	2	0
Cross Over (Placebo to AA) Started other prostate cancer treatment	0	0	8
Cross Over (Placebo to AA) Ongoing	0	0	35
Cross Over (Placebo to AA) Adverse Event	0	0	9
Cross Over (Placebo to AA) Withdrawal by Subject	0	0	2
Cross Over (Placebo to AA) Progressive disease	0	0	20
Cross Over (Placebo to AA) Other	0	0	19

Baseline Characteristics

Abiraterone Acetate in Asymptomatic or Mildly Symptomatic Patients With Metastatic Castration-Resistant Prostate Cancer

Baseline characteristics by cohort

Measure	Abiraterone Acetate + Prednisone (AAP) n=546 Participants Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4\*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo n=542 Participants Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Total n=1088 Participants Total of all reporting groups
Age, Continuous	70.5 years STANDARD_DEVIATION 8.8 • n=5 Participants	70.1 years STANDARD_DEVIATION 8.72 • n=7 Participants	70.3 years STANDARD_DEVIATION 8.76 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	546 Participants n=5 Participants	542 Participants n=7 Participants	1088 Participants n=5 Participants
Region of Enrollment Australia	60 Participants n=5 Participants	72 Participants n=7 Participants	132 Participants n=5 Participants
Region of Enrollment Belgium	25 Participants n=5 Participants	17 Participants n=7 Participants	42 Participants n=5 Participants
Region of Enrollment Canada	63 Participants n=5 Participants	37 Participants n=7 Participants	100 Participants n=5 Participants
Region of Enrollment France	24 Participants n=5 Participants	29 Participants n=7 Participants	53 Participants n=5 Participants
Region of Enrollment Germany	46 Participants n=5 Participants	32 Participants n=7 Participants	78 Participants n=5 Participants
Region of Enrollment Greece	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment Italy	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Netherlands	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment Spain	25 Participants n=5 Participants	20 Participants n=7 Participants	45 Participants n=5 Participants
Region of Enrollment Sweden	4 Participants n=5 Participants	13 Participants n=7 Participants	17 Participants n=5 Participants
Region of Enrollment United Kingdom	42 Participants n=5 Participants	56 Participants n=7 Participants	98 Participants n=5 Participants
Region of Enrollment United States	234 Participants n=5 Participants	238 Participants n=7 Participants	472 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization (Day 1) up to end of study (Month 60)

Population: Intent-to-treat (ITT) population included all the randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.

Overall survival is defined as the time from randomization to date of death from any cause.

Outcome measures

Measure	Abiraterone Acetate + Prednisone (AAP) n=546 Participants Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4\*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo n=542 Participants Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo to Abiraterone Acetate Participants received initially placebo along with prednisone 5 mg tablet, orally, later on switched to 1,000 milligram (mg) abiraterone acetate tablet (as 4\*250 mg tablets) along with prednisone 5 mg tablet due to disease progression.
Overall Survival	34.66 Months Interval 32.72 to 36.8	30.29 Months Interval 28.65 to 33.28	—

PRIMARY outcome

Timeframe: From randomization (Day 1) up to first radiographic progression or cutoff date (Month 18)

Population: ITT population included all the randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.

The rPFS was defined as the time from randomization to the occurrence of one of the following: 1) a participant was considered to have progressed by bone scan if - a) the first bone scan with greater than or equal to (>=) 2 new lesions compared to baseline was observed in less than (<) 12 weeks from randomization and was confirmed by a second bone scan taken >=6 weeks later showing >=2 additional new lesions (a total of >=4 new lesions compared to baseline), b) the first bone scan with >=2 new lesions compared to baseline was observed in >=12 weeks from randomization and the new lesions were verified on the next bone scan >=6 weeks later (a total of >=2 new lesions compared to baseline); 2) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI); 3) death from any cause.

Outcome measures

Measure	Abiraterone Acetate + Prednisone (AAP) n=546 Participants Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4\*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo n=542 Participants Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo to Abiraterone Acetate Participants received initially placebo along with prednisone 5 mg tablet, orally, later on switched to 1,000 milligram (mg) abiraterone acetate tablet (as 4\*250 mg tablets) along with prednisone 5 mg tablet due to disease progression.
Radiographic Progression-free Survival (rPFS)	NA Months Interval 11.66 to Data was not estimable due to insufficient number of participants who had the event.	8.28 Months Interval 8.12 to 8.54	—

SECONDARY outcome

Timeframe: From randomization (Day 1) up to first opiate use or end of study (Month 60)

Population: ITT population included all the randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.

The time interval from the date of randomization to the date of opiate use for cancer pain. Participants who have no opiate use at the time of analysis were censored at the last known date of no opiate use for cancer pain. Participants with no assessment were censored at the date of randomization.

Outcome measures

Measure	Abiraterone Acetate + Prednisone (AAP) n=546 Participants Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4\*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo n=542 Participants Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo to Abiraterone Acetate Participants received initially placebo along with prednisone 5 mg tablet, orally, later on switched to 1,000 milligram (mg) abiraterone acetate tablet (as 4\*250 mg tablets) along with prednisone 5 mg tablet due to disease progression.
Time to Opiate Use for Prostate Cancer Pain	33.38 Months Interval 30.23 to 39.75	23.39 Months Interval 20.27 to 27.53	—

SECONDARY outcome

Timeframe: From randomization (Day 1) up to initiation of cytotoxic chemotherapy or cutoff date (Month 18)

Population: ITT population included all the randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.

The time interval from the date of randomization to the date of initiation of cytotoxic chemotherapy for prostate cancer. Participants who had no cytotoxic chemotherapy administration at the time of analysis were censored at the last known date when no cytotoxic chemotherapy was administered. Participants with no assessment were censored at the date of randomization.

Outcome measures

Measure	Abiraterone Acetate + Prednisone (AAP) n=546 Participants Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4\*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo n=542 Participants Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo to Abiraterone Acetate Participants received initially placebo along with prednisone 5 mg tablet, orally, later on switched to 1,000 milligram (mg) abiraterone acetate tablet (as 4\*250 mg tablets) along with prednisone 5 mg tablet due to disease progression.
Time to Initiation of Cytotoxic Chemotherapy	25.17 Months Interval 23.26 to Upper limit was not estimable due to insufficient number of participants who had the event.	16.82 Months Interval 14.55 to 19.38	—

SECONDARY outcome

Timeframe: From randomization (Day 1) up to first radiographic progression or cutoff date (Month 18)

Population: ITT population included all the randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.

The time interval from the date of randomization to the first date at which there was at least a 1 grade change (worsening) in the ECOG performance status grade. Participants who had no deterioration in ECOG performance status grade at the time of the analysis were censored at the last known date of no deterioration. ECOG is a 5-point scale, where 0=Fully active, 1=Ambulatory, carry out work of sedentary nature, 2=Ambulatory, capable of all self-care, 3=Capable of limited self-care, confined to bed or chair more than 50% of waking hours, 4=Completely disabled, no self-care, totally confined to bed or chair, 5=Dead. Participants with no assessment were censored at the date of randomization.

Outcome measures

Measure	Abiraterone Acetate + Prednisone (AAP) n=546 Participants Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4\*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo n=542 Participants Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo to Abiraterone Acetate Participants received initially placebo along with prednisone 5 mg tablet, orally, later on switched to 1,000 milligram (mg) abiraterone acetate tablet (as 4\*250 mg tablets) along with prednisone 5 mg tablet due to disease progression.
Time to Deterioration in Eastern Cooperative Oncology Group (ECOG) Performance Score by >=1 Point	12.29 Months Interval 11.33 to 14.29	10.87 Months Interval 9.49 to 11.76	—

SECONDARY outcome

Timeframe: From randomization (Day 1) up to date of PSA progerssion or cutoff date (Month 18)

Population: ITT population included all the randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.

The time interval from the date of randomization to the date of PSA progression as defined in the protocol-specific prostate cancer Working Group 2 (PCWG2) criteria. A participant was considered to have a PSA progression if the PSA level had a 25 percent (%) or greater increase from nadir and an absolute increase of 2 nanogram/milliliter ((ng/mL) or more, which is confirmed by a second value obtained in 3 or more weeks. Participants who had no PSA progression at the time of the analysis were censored at the last known date of no PSA progression. Participants with no on-study PSA assessment or no baseline PSA assessment were censored at the date of randomization.

Outcome measures

Measure	Abiraterone Acetate + Prednisone (AAP) n=546 Participants Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4\*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo n=542 Participants Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo to Abiraterone Acetate Participants received initially placebo along with prednisone 5 mg tablet, orally, later on switched to 1,000 milligram (mg) abiraterone acetate tablet (as 4\*250 mg tablets) along with prednisone 5 mg tablet due to disease progression.
Time to Prostate-specific Antigen (PSA) Progression	11.07 Months Interval 8.51 to 11.24	5.55 Months Interval 5.39 to 5.59	—

SECONDARY outcome

Timeframe: From first dose of study drug up to 30 days after the last dose of study drug

Population: Safety analysis set included all participants in the randomized population who received any study drug.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and up to 30 days after last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state.

Outcome measures

Measure	Abiraterone Acetate + Prednisone (AAP) n=542 Participants Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4\*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo n=540 Participants Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo to Abiraterone Acetate n=93 Participants Participants received initially placebo along with prednisone 5 mg tablet, orally, later on switched to 1,000 milligram (mg) abiraterone acetate tablet (as 4\*250 mg tablets) along with prednisone 5 mg tablet due to disease progression.
Number of Participants With Treatment Emergent Adverse Events With Treatment-Emergent Adverse Events	541 Participants	524 Participants	93 Participants
Number of Participants With Treatment Emergent Adverse Events With Treatment-Emergent Serious Adverse Events	208 Participants	148 Participants	39 Participants

SECONDARY outcome

Timeframe: Up to Cycle 5, Day 1

Population: Data was not reported as non-compartmental analysis was not performed due to sparse sampling.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Cycle 5, Day 1

Population: Data was not reported as non-compartmental analysis was not performed due to sparse sampling.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Cycle 5, Day 1

Population: Data was not reported as non-compartmental analysis was not performed due to sparse sampling.

The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Cycle 5, Day 1

Population: Data was not reported as non-compartmental analysis was not performed due to sparse sampling.

The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).

Outcome measures

Outcome data not reported

Adverse Events

Abiraterone Acetate + Prednisone (AAP)

Serious events: 215 serious events

Other events: 530 other events

Deaths: 0 deaths

Placebo

Serious events: 156 serious events

Other events: 505 other events

Deaths: 0 deaths

Placebo to AA

Serious events: 40 serious events

Other events: 86 other events

Deaths: 0 deaths

Serious adverse events

Measure	Abiraterone Acetate + Prednisone (AAP) n=542 participants at risk Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4\*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo n=540 participants at risk Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo to AA n=93 participants at risk Participants who were originally assigned to placebo were later on switched to 1,000 milligram (mg) abiraterone acetate tablet (as 4\*250 mg tablets) along with prednisone 5 mg tablet.
Respiratory, thoracic and mediastinal disorders Acute Pulmonary Oedema	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Respiratory, thoracic and mediastinal disorders Lung Disorder	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.56% 3/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Respiratory, thoracic and mediastinal disorders Pneumonia Aspiration	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	1.8% 10/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	2.2% 12/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Urinary Tract Obstruction	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Reproductive system and breast disorders Erectile Dysfunction	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Reproductive system and breast disorders Prostatic Haemorrhage	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Reproductive system and breast disorders Scrotal Pain	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Blood and lymphatic system disorders Anaemia	1.5% 8/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 6/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Blood and lymphatic system disorders Coagulopathy	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Blood and lymphatic system disorders Thrombocytopenia	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Tachyarrhythmia	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Ear and labyrinth disorders Hypoacusis	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Ear and labyrinth disorders Vertigo	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Colitis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Constipation	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Diarrhoea	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Dyspepsia	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Gastritis	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Ileus	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Melaena	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Nausea	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Pancreatitis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Periodontitis	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Peritonitis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Vomiting	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Asthenia	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Fatigue	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	2.2% 2/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Malaise	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Pain	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Pyrexia	0.55% 3/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.56% 3/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Hepatobiliary disorders Cholecystitis	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Hepatobiliary disorders Cholelithiasis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Hepatobiliary disorders Jaundice	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Bacteraemia	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Bronchitis	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Bronchopneumonia	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Cellulitis	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.56% 3/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	2.2% 2/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Cystitis	0.55% 3/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Gastroenteritis	1.1% 6/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Infection	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Influenza	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Osteomyelitis	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Pneumonia	1.8% 10/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.74% 4/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Pyelonephritis	0.55% 3/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Sepsis	1.3% 7/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Sinusitis	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Tracheobronchitis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Urosepsis	0.55% 3/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Fall	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Investigations Colonoscopy	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Metabolism and nutrition disorders Anorexia	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Metabolism and nutrition disorders Dehydration	1.1% 6/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Metabolism and nutrition disorders Hyperuricaemia	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Metabolism and nutrition disorders Hypokalaemia	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Metabolism and nutrition disorders Hyponatraemia	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.74% 4/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Arthritis	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Osteitis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Convulsion	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Dizziness	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Epilepsy	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Monoparesis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Paraesthesia	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Paraparesis	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Paraplegia	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Presyncope	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Quadriparesis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Sciatica	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Syncope	1.1% 6/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders VIth nerve paralysis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Psychiatric disorders Agitation	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Psychiatric disorders Delirium	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Dysuria	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Haematuria	2.0% 11/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.93% 5/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	3.2% 3/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Hydronephrosis	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.74% 4/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Nephrolithiasis	0.55% 3/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Pollakiuria	0.55% 3/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Reproductive system and breast disorders Prostatomegaly	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.93% 5/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.55% 3/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Skin and subcutaneous tissue disorders Lentigo	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Surgical and medical procedures Chemotherapy	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Surgical and medical procedures Pancreatectomy	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Vascular disorders Hypertension	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.56% 3/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Vascular disorders Hypotension	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Vascular disorders Thrombophlebitis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Vascular disorders Thrombosis	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Blood and lymphatic system disorders Disseminated Intravascular Coagulation	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Blood and lymphatic system disorders Febrile Neutropenia	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Acute Coronary Syndrome	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Acute Myocardial Infarction	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Angina Pectoris	1.1% 6/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Atrial Fibrillation	2.0% 11/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.5% 8/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Atrioventricular Block	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Atrioventricular Block Second Degree	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Bifascicular Block	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Cardiac Arrest	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Cardiac Disorder	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Cardiac Failure	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Cardiac Failure Congestive	0.55% 3/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Conduction Disorder	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Coronary Artery Disease	0.74% 4/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Ischaemic Cardiomyopathy	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Myocardial Infarction	0.74% 4/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.93% 5/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	2.2% 2/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Myocardial Ischaemia	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Supraventricular Tachyarrhythmia	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Cardiac disorders Supraventricular Tachycardia	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Endocrine disorders Adrenal Insufficiency	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Abdominal Pain	0.55% 3/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.93% 5/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Abdominal Pain Lower	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Abdominal Pain Upper	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Diverticular Perforation	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Diverticulum Intestinal	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Diverticulum Intestinal Haemorrhagic	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Enterovesical Fistula	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Food Poisoning	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Gastric Ulcer	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Gastritis Erosive	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Gastrointestinal Necrosis	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Gastrooesophageal Reflux Disease	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Intestinal Ischaemia	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Intestinal Obstruction	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Oesophageal Mass	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Pancreatic Disorder	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Pancreatitis Necrotising	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Small Intestinal Obstruction	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Upper Gastrointestinal Haemorrhage	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Varices Oesophageal	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Catheter Related Complication	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Chest Pain	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Death	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Disease Progression	1.5% 8/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.74% 4/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	6.5% 6/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Gait Disturbance	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders General Physical Health Deterioration	1.3% 7/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Hypothermia	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Mucosal Inflammation	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Multi-Organ Failure	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Non-Cardiac Chest Pain	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.74% 4/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Oedema Peripheral	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Performance Status Decreased	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Systemic Inflammatory Response Syndrome	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Hepatobiliary disorders Bile Duct Obstruction	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Anal Abscess	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Arthritis Bacterial	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Biliary Sepsis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Bursitis Infective	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Campylobacter Gastroenteritis	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Enterococcal Infection	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Escherichia Urinary Tract Infection	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Febrile Infection	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Gallbladder Abscess	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Gastroenteritis Salmonella	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Gastroenteritis Viral	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Gastrointestinal Infection	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Gingival Infection	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Herpes Zoster	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Infected Skin Ulcer	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Infective Exacerbation of Chronic Obstructive Airways Disease	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Lower Respiratory Tract Infection	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Lung Infection	0.55% 3/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Necrotising Fasciitis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Parainfluenzae Virus Infection	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Pneumonia Influenzal	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Pneumonia Staphylococcal	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Postoperative Wound Infection	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Pseudomonal Bacteraemia	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Respiratory Tract Infection	0.55% 3/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Skin Infection	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Staphylococcal Infection	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Urinary Tract Infection	2.6% 14/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.74% 4/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	5.4% 5/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Urinary Tract Infection Bacterial	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Viral Infection	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Wound Infection	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Animal Scratch	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Ankle Fracture	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Bladder Perforation	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Cataract Operation Complication	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Cystitis Radiation	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Device Dislocation	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Femoral Neck Fracture	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Femur Fracture	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Gastroenteritis Radiation	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Gastrointestinal Anastomotic Leak	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Implantable Defibrillator Malfunction	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Multiple Fractures	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Multiple Injuries	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Narcotic Intoxication	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Procedural Pain	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Pubic Rami Fracture	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Scapula Fracture	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Skeletal Injury	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Skin Laceration	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Skull Fracture	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Soft Tissue Injury	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Spinal Compression Fracture	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Spinal Fracture	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Stress Fracture	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Subdural Haematoma	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	2.2% 2/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Subdural Haemorrhage	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Tendon Rupture	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Thoracic Vertebral Fracture	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Tibia Fracture	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Wrist Fracture	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Investigations Alanine Aminotransferase Increased	0.92% 5/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Investigations Aspartate Aminotransferase Increased	0.55% 3/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Investigations Blood Creatinine Increased	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Investigations Blood Uric Acid Increased	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Investigations Electrocardiogram QT Prolonged	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Investigations Electrocardiogram St Segment Depression	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Investigations Lipase Increased	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Investigations Platelet Count Decreased	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Metabolism and nutrition disorders Failure to Thrive	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Metabolism and nutrition disorders Fluid Retention	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Back Pain	1.1% 6/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.74% 4/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Bone Pain	0.74% 4/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.93% 5/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Flank Pain	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Groin Pain	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Jaw Cyst	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Joint Swelling	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Lumbar Spinal Stenosis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Muscular Weakness	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Pain in Extremity	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	2.2% 2/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Pathological Fracture	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Rotator Cuff Syndrome	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Spinal Column Stenosis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-Cell Type Acute Leukaemia	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal Cell Carcinoma	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder Cancer	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder Transitional Cell Carcinoma	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer Pain	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Central Nervous System Lymphoma	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic Lymphocytic Leukaemia	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Adenoma	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Cancer	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal Cancer	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric Cancer	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intestinal Adenocarcinoma	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Adenocarcinoma	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Neoplasm	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Neoplasm Malignant	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Melanoma	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Neoplasm of Ampulla of Vater	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Meninges	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic Pain	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic Carcinoma	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous Cell Carcinoma	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Urethral Cancer	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Amyotrophic Lateral Sclerosis	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Carotid Artery Stenosis	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Cerebral Haemorrhage	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Cerebral Infarction	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Cerebral Ischaemia	0.55% 3/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Cerebrovascular Accident	1.1% 6/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Embolic Stroke	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Loss of Consciousness	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Memory Impairment	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Migraine with Aura	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Nerve Root Compression	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Neurological Symptom	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Spinal Cord Compression	1.3% 7/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.74% 4/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Syncope Vasovagal	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Transient Ischaemic Attack	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Psychiatric disorders Completed Suicide	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Psychiatric disorders Confusional State	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Bladder Mass	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Bladder Obstruction	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Bladder Spasm	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Bladder Tamponade	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Calculus Bladder	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	2.2% 2/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Calculus Ureteric	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Haemorrhage Urinary Tract	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Obstructive Uropathy	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Renal Colic	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Renal Failure	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.56% 3/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Renal Failure Acute	0.55% 3/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Renal Impairment	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Ureteric Obstruction	0.37% 2/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Ureteric Stenosis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Urethral Obstruction	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Urethral Stenosis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Urinary Incontinence	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Urinary Retention	1.1% 6/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.56% 3/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Respiratory, thoracic and mediastinal disorders Tonsillar Cyst	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Skin and subcutaneous tissue disorders Actinic Keratosis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Skin and subcutaneous tissue disorders Skin Lesion	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Surgical and medical procedures Aortic Valve Replacement	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Surgical and medical procedures Knee Arthroplasty	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Surgical and medical procedures Transurethral Prostatectomy	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Vascular disorders Arterial Thrombosis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Vascular disorders Deep Vein Thrombosis	0.74% 4/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.37% 2/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Vascular disorders Embolism Venous	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Vascular disorders Hypertensive Crisis	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Vascular disorders Orthostatic Hypotension	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Vascular disorders Peripheral Embolism	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Vascular disorders Peripheral Vascular Disorder	0.18% 1/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Vascular disorders Venous Thrombosis	0.00% 0/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.19% 1/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.

Other adverse events

Measure	Abiraterone Acetate + Prednisone (AAP) n=542 participants at risk Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4\*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo n=540 participants at risk Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.	Placebo to AA n=93 participants at risk Participants who were originally assigned to placebo were later on switched to 1,000 milligram (mg) abiraterone acetate tablet (as 4\*250 mg tablets) along with prednisone 5 mg tablet.
Blood and lymphatic system disorders Anaemia	10.9% 59/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	9.8% 53/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	12.9% 12/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Constipation	26.6% 144/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	20.7% 112/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	16.1% 15/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Diarrhoea	24.9% 135/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	18.1% 98/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	14.0% 13/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Dyspepsia	11.4% 62/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	5.2% 28/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Nausea	26.6% 144/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	23.5% 127/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	16.1% 15/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Vomiting	15.9% 86/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	11.3% 61/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	12.9% 12/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Asthenia	8.5% 46/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	8.5% 46/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Fatigue	44.8% 243/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	37.0% 200/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	29.0% 27/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Pyrexia	10.0% 54/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	6.1% 33/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	5.4% 5/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Bronchitis	6.3% 34/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	2.6% 14/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Nasopharyngitis	12.0% 65/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	8.5% 46/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	5.4% 5/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Sinusitis	5.4% 29/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.93% 5/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	3.2% 3/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Contusion	14.9% 81/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	9.1% 49/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	6.5% 6/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Fall	8.7% 47/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	3.7% 20/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	12.9% 12/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Metabolism and nutrition disorders Anorexia	10.3% 56/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	7.4% 40/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	10.8% 10/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Metabolism and nutrition disorders Hyperglycaemia	9.6% 52/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	7.6% 41/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	6.5% 6/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Metabolism and nutrition disorders Hypokalaemia	18.3% 99/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	12.6% 68/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	9.7% 9/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Metabolism and nutrition disorders Hyponatraemia	2.6% 14/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	2.8% 15/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	5.4% 5/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Arthralgia	31.7% 172/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	24.3% 131/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	20.4% 19/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Myalgia	7.4% 40/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	5.9% 32/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	3.2% 3/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Dizziness	14.9% 81/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	13.5% 73/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	7.5% 7/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Headache	15.9% 86/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	12.2% 66/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	9.7% 9/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Psychiatric disorders Anxiety	5.5% 30/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	4.3% 23/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	4.3% 4/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Psychiatric disorders Depression	5.9% 32/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	3.5% 19/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	3.2% 3/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Psychiatric disorders Insomnia	15.1% 82/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	11.5% 62/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	5.4% 5/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Haematuria	10.3% 56/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	5.9% 32/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	4.3% 4/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Nocturia	7.0% 38/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	5.4% 29/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Pollakiuria	10.3% 56/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	10.2% 55/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	2.2% 2/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Respiratory, thoracic and mediastinal disorders Cough	19.6% 106/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	13.7% 74/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	11.8% 11/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.1% 71/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	9.6% 52/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	7.5% 7/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Skin and subcutaneous tissue disorders Rash	9.0% 49/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	3.9% 21/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 1/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Vascular disorders Hypertension	23.8% 129/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	13.5% 73/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	6.5% 6/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Gastrointestinal disorders Abdominal Pain	9.0% 49/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	8.1% 44/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	5.4% 5/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
General disorders Oedema Peripheral	27.3% 148/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	22.0% 119/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	23.7% 22/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Lower Respiratory Tract Infection	2.2% 12/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	2.4% 13/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	5.4% 5/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Upper Respiratory Tract Infection	13.7% 74/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	8.0% 43/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	4.3% 4/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Infections and infestations Urinary Tract Infection	9.0% 49/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	7.4% 40/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	11.8% 11/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Injury, poisoning and procedural complications Skin Laceration	2.4% 13/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	2.8% 15/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	6.5% 6/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Investigations Alanine Aminotransferase Increased	12.9% 70/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	4.8% 26/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	3.2% 3/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Investigations Aspartate Aminotransferase Increased	11.6% 63/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	4.6% 25/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	4.3% 4/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Investigations Weight Decreased	7.7% 42/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	5.0% 27/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	6.5% 6/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Investigations Weight Increased	5.4% 29/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	7.4% 40/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	2.2% 2/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Metabolism and nutrition disorders Decreased Appetite	5.2% 28/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	5.6% 30/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Back Pain	36.7% 199/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	33.3% 180/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	28.0% 26/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Bone Pain	26.6% 144/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	20.7% 112/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	15.1% 14/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Groin Pain	7.6% 41/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	4.1% 22/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Muscle Spasms	14.4% 78/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	20.6% 111/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	2.2% 2/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Muscular Weakness	6.5% 35/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	7.8% 42/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	5.4% 5/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	17.9% 97/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	14.3% 77/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	12.9% 12/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Neck Pain	5.5% 30/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	3.1% 17/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	2.2% 2/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Musculoskeletal and connective tissue disorders Pain in Extremity	19.7% 107/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	16.5% 89/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	17.2% 16/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Nervous system disorders Neuropathy Peripheral	2.2% 12/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	1.1% 6/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	7.5% 7/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Renal and urinary disorders Urinary Incontinence	6.8% 37/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	4.6% 25/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	0.00% 0/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.
Vascular disorders Hot Flush	22.9% 124/542 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	18.5% 100/540 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.	6.5% 6/93 • From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years) Safety analysis set included all participants in the randomized population who received any study drug.

Additional Information

SENIOR DIRECTOR CLINICAL RESEARCH

Janssen R&D US

Email: ClinicalTrialDisclosure@its.jnj.com

Results disclosure agreements

• Principal investigator is a sponsor employee A copy of the manuscript must be provided to the Sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
• Publication restrictions are in place

Restriction type: OTHER