Trial Outcomes & Findings for An Efficacy and Safety Study of Tocilizumab (RoActemra/Actemra) in Participants With Giant Cell Arteritis (GCA) (NCT NCT01791153)

NCT ID: NCT01791153

Last Updated: 2020-02-06

Results Overview

Remission was defined as the absence of flare and normalization of the C-reactive protein (CRP) (less than \[\<\] 1 milligram per deciliter \[mg/dL\]). Sustained remission was defined as the absence of flare following induction of remission within 12 weeks of randomization and maintained up to Week 52. Flare was determined by the investigator and was defined as the recurrence of signs or symptoms of GCA and/or erythrocyte sedimentation rate (ESR) greater than or equal to (\>/=) 30 millimeters per hour (mm/hr) attributable to GCA. A single CRP elevation (\>/=1 mg/dL) was not considered as a sign of flare, unless the CRP remained elevated (\>/=1 mg/dL) at the next study visit.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 251 participants
• Primary outcome timeframe: Week 52
• Results posted on: 2020-02-06

Participant Flow

The study consists of 2 parts: a 52-week double-blind treatment period (Part 1) followed by a 104-week open label long-term follow-up period (Part 2).

Of the 363 participants screened, a total of 251 participants were randomized into the study. One participant who was randomized to the "Tocilizumab q2w + 26 weeks prednisone taper" group withdrew on the same day of randomization and did not receive any study treatment. This participant was not included in any of the study analyses.

Participant milestones

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Participants received tocilizumab at a dose of 162 milligrams (mg) as subcutaneous (SC) injection every week (qw) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Participants received tocilizumab at a dose of 162 mg as SC injection every 2 weeks (q2w) (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.	Part 2: No Tocilizumab (Placebo in Part 1) Participants did not receive tocilizumab in Part 2 from Week 52 up to Week 156. These participants received placebo during Part 1 (Weeks 1 to 52).	Part 2: No Tocilizumab (Tocilizumab in Part 1) Participants did not receive tocilizumab in Part 2 from Week 52 up to Week 156. These participants received tocilizumab during Part 1 (Weeks 1 to 52).	Part 2: Tocilizumab (Placebo in Part 1) Participants received open-label tocilizumab as determined by the investigator during Part 2 of the study (from Week 52 up to Week 156). These participants received placebo during Part 1 (Weeks 1 to 52).	Part 2: Tocilizumab (Tocilizumab in Part 1) Participants received open-label tocilizumab as determined by the investigator during Part 2 of the study (from Week 52 up to Week 156). These participants received tocilizumab during Part 1 (Weeks 1 to 52).
Part 1: Blinded Period STARTED	100	49	50	51	0	0	0	0
Part 1: Blinded Period COMPLETED	85	41	44	46	0	0	0	0
Part 1: Blinded Period NOT COMPLETED	15	8	6	5	0	0	0	0
Part 2: Open-label Period STARTED	0	0	0	0	40	58	50	67
Part 2: Open-label Period COMPLETED	0	0	0	0	38	54	44	61
Part 2: Open-label Period NOT COMPLETED	0	0	0	0	2	4	6	6

Reasons for withdrawal

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Participants received tocilizumab at a dose of 162 milligrams (mg) as subcutaneous (SC) injection every week (qw) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Participants received tocilizumab at a dose of 162 mg as SC injection every 2 weeks (q2w) (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.	Part 2: No Tocilizumab (Placebo in Part 1) Participants did not receive tocilizumab in Part 2 from Week 52 up to Week 156. These participants received placebo during Part 1 (Weeks 1 to 52).	Part 2: No Tocilizumab (Tocilizumab in Part 1) Participants did not receive tocilizumab in Part 2 from Week 52 up to Week 156. These participants received tocilizumab during Part 1 (Weeks 1 to 52).	Part 2: Tocilizumab (Placebo in Part 1) Participants received open-label tocilizumab as determined by the investigator during Part 2 of the study (from Week 52 up to Week 156). These participants received placebo during Part 1 (Weeks 1 to 52).	Part 2: Tocilizumab (Tocilizumab in Part 1) Participants received open-label tocilizumab as determined by the investigator during Part 2 of the study (from Week 52 up to Week 156). These participants received tocilizumab during Part 1 (Weeks 1 to 52).
Part 1: Blinded Period Adverse Event	7	3	2	0	0	0	0	0
Part 1: Blinded Period Lack of Efficacy	1	3	2	2	0	0	0	0
Part 1: Blinded Period Non-Compliance	1	0	0	0	0	0	0	0
Part 1: Blinded Period Physician Decision	0	0	0	1	0	0	0	0
Part 1: Blinded Period Protocol Violation	0	0	0	1	0	0	0	0
Part 1: Blinded Period Withdrawal by Subject	6	2	2	1	0	0	0	0
Part 2: Open-label Period Adverse Event	0	0	0	0	0	1	1	2
Part 2: Open-label Period Death	0	0	0	0	0	1	1	1
Part 2: Open-label Period Lost to Follow-up	0	0	0	0	0	0	1	0
Part 2: Open-label Period Lack of Efficacy	0	0	0	0	0	0	0	1
Part 2: Open-label Period Withdrawal by Subject	0	0	0	0	1	1	3	2
Part 2: Open-label Period Physician Decision	0	0	0	0	1	1	0	0

Baseline Characteristics

An Efficacy and Safety Study of Tocilizumab (RoActemra/Actemra) in Participants With Giant Cell Arteritis (GCA)

Baseline characteristics by cohort

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=100 Participants Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper n=50 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper n=51 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.	Total n=250 Participants Total of all reporting groups
Age, Continuous	69.5 years STANDARD_DEVIATION 8.50 • n=5 Participants	69.4 years STANDARD_DEVIATION 8.29 • n=7 Participants	69.3 years STANDARD_DEVIATION 8.14 • n=5 Participants	67.8 years STANDARD_DEVIATION 7.70 • n=4 Participants	69.1 years STANDARD_DEVIATION 8.21 • n=21 Participants
Sex: Female, Male Female	78 Participants n=5 Participants	34 Participants n=7 Participants	38 Participants n=5 Participants	37 Participants n=4 Participants	187 Participants n=21 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	15 Participants n=7 Participants	12 Participants n=5 Participants	14 Participants n=4 Participants	63 Participants n=21 Participants

PRIMARY outcome

Timeframe: Week 52

Population: Intent-to-treat (ITT) population included all participants randomized into the study who received at least one administration of study drug.

Remission was defined as the absence of flare and normalization of the C-reactive protein (CRP) (less than [<] 1 milligram per deciliter [mg/dL]). Sustained remission was defined as the absence of flare following induction of remission within 12 weeks of randomization and maintained up to Week 52. Flare was determined by the investigator and was defined as the recurrence of signs or symptoms of GCA and/or erythrocyte sedimentation rate (ESR) greater than or equal to (>/=) 30 millimeters per hour (mm/hr) attributable to GCA. A single CRP elevation (>/=1 mg/dL) was not considered as a sign of flare, unless the CRP remained elevated (>/=1 mg/dL) at the next study visit.

Outcome measures

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=100 Participants Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper n=50 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 26 Weeks Prednisone Taper)	56.0 percentage of participants	53.1 percentage of participants	14.0 percentage of participants	—

SECONDARY outcome

Timeframe: Week 52

Population: ITT population

Remission was defined as the absence of flare and normalization of the CRP (<1 mg/dL). Sustained remission was defined as the absence of flare following induction of remission within 12 weeks of randomization and maintained up to Week 52. Flare was determined by the investigator and was defined as the recurrence of signs or symptoms of GCA and/or ESR >/=30 mm/hr attributable to GCA. A single CRP elevation (>/=1 mg/dL) was not considered as a sign of flare, unless the CRP remained elevated (>/=1 mg/dL) at the next study visit.

Outcome measures

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=100 Participants Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper n=51 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 52 Weeks Prednisone Taper)	56.0 percentage of participants	53.1 percentage of participants	17.6 percentage of participants	—

SECONDARY outcome

Timeframe: Up to 52 weeks

Population: ITT population

Flare was determined by the investigator and was defined as the recurrence of signs or symptoms of GCA and/or ESR >/=30 mm/hr attributable to GCA. Participants who withdrew from the study prior to Week 52 were censored from the time of withdrawal.

Outcome measures

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=100 Participants Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper n=50 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper n=51 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Time to First GCA Disease Flare	NA days Data could not be calculated due to low number of participants who had an event.	NA days Data could not be calculated due to low number of participants who had an event.	165.0 days Interval 120.0 to 260.0	295.0 days Interval 168.0 to Data could not be calculated due to low number of participants who had an event.

SECONDARY outcome

Timeframe: Up to 52 weeks

Population: ITT Population

The median total cumulative prednisone dose over the 52 weeks for each treatment group and the corresponding 95% confidence intervals are presented.

Outcome measures

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=100 Participants Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper n=50 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper n=51 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Total Cumulative Prednisone Dose	1862.00 milligrams (mg) Interval 1582.0 to 1942.0	1862.00 milligrams (mg) Interval 1568.0 to 2239.5	3296.00 milligrams (mg) Interval 2729.5 to 4023.5	3817.50 milligrams (mg) Interval 2817.5 to 4425.5

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT population. Here, 'Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.

The SF-36 is a standardized questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical Component Score (PCS) and Mental Component Score (MCS). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). A positive change from baseline indicates improvement. No imputation was used for missing data. Data was set to missing for participants who received escape therapy.

Outcome measures

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=97 Participants Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper n=48 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 PCS: Baseline (n=97,49,48,49)	43.10 units on a scale Standard Deviation 9.43	40.62 units on a scale Standard Deviation 8.00	42.65 units on a scale Standard Deviation 10.87	41.12 units on a scale Standard Deviation 9.97
Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 PCS: Change at Week 52 (n=59,26,9,18)	5.37 units on a scale Standard Deviation 7.38	2.71 units on a scale Standard Deviation 8.86	2.08 units on a scale Standard Deviation 12.11	-2.80 units on a scale Standard Deviation 6.98
Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 MCS: Baseline (n=97,49,48,49)	42.77 units on a scale Standard Deviation 12.43	47.67 units on a scale Standard Deviation 12.59	42.73 units on a scale Standard Deviation 12.13	40.45 units on a scale Standard Deviation 13.73
Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 MCS: Change at Week 52 (n=59,26,9,18)	8.21 units on a scale Standard Deviation 10.35	1.98 units on a scale Standard Deviation 7.17	4.99 units on a scale Standard Deviation 7.54	2.60 units on a scale Standard Deviation 10.56

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT population. Here, 'Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.

Participants assessed their current disease activity on a 0-100 millimeter (mm) VAS, where 0 mm = no disease activity and 100 mm = maximum disease activity. A negative change from baseline indicates improvement.

Outcome measures

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=100 Participants Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper n=51 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52 Baseline (n=100,49,49,51)	43.61 mm Standard Deviation 25.66	46.65 mm Standard Deviation 25.60	35.73 mm Standard Deviation 28.15	47.78 mm Standard Deviation 27.80
Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52 Change at Week 52 (n=60,26,11,18)	-19.68 mm Standard Deviation 33.64	-22.69 mm Standard Deviation 22.41	-8.45 mm Standard Deviation 24.81	-10.00 mm Standard Deviation 35.12

SECONDARY outcome

Timeframe: Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0])

Population: Pharmacokinetics (PK)-evaluable population included all participants who received at least one tocilizumab injection and had at least one PK sample with detectable results taken at any time during the study.

AUCtau is the model-predicted area under the tocilizumab serum concentration versus time curve from time zero to the end of dosing interval. AUCtau is measured in microgram*day per milliliter (mcg*day/mL).

Outcome measures

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=100 Participants Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Steady State of Tocilizumab	499.2 mcg*day/mL Standard Deviation 210.4	227.2 mcg*day/mL Standard Deviation 165.4	—	—

SECONDARY outcome

Timeframe: Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0])

Population: PK-evaluable population

Cmax,ss is maximum model-predicted serum steady state concentration of tocilizumab measured in micrograms per milliliter (mcg/mL).

Outcome measures

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=100 Participants Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Maximum Serum Concentration at Steady State (Cmax,ss) of Tocilizumab	73 mcg/mL Standard Deviation 30.4	19.3 mcg/mL Standard Deviation 12.8	—	—

SECONDARY outcome

Timeframe: Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0])

Population: PK-evaluable population

Cmin,ss is minimum model-predicted serum steady state concentration of tocilizumab measured in mcg/mL.

Outcome measures

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=100 Participants Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Minimum Serum Concentration at Steady State (Cmin,ss) of Tocilizumab	68.1 mcg/mL Standard Deviation 29.5	11.1 mcg/mL Standard Deviation 10.3	—	—

SECONDARY outcome

Timeframe: Predose (Hour 0) at Baseline and Week 52

Population: PK-evaluable population. Here, 'Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.

Ctrough is minimum observed serum concentration of tocilizumab measured in mcg/mL.

Outcome measures

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=99 Participants Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=48 Participants Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Minimum Observed Serum Concentration (Ctrough) of Tocilizumab Baseline (n= 99, 48)	0.07 mcg/mL Standard Deviation 0.72	0.00 mcg/mL Standard Deviation 0.02	—	—
Minimum Observed Serum Concentration (Ctrough) of Tocilizumab Week 52 (n= 72, 33)	67.93 mcg/mL Standard Deviation 34.40	12.22 mcg/mL Standard Deviation 10.02	—	—

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Safety population. Here, 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.

Outcome measures

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=100 Participants Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper n=50 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper n=51 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Serum Interleukin-6 (IL-6) Level Baseline (n=91,44,50,47)	8.79 picograms per milliliter (pg/mL) Standard Deviation 10.01	16.29 picograms per milliliter (pg/mL) Standard Deviation 31.23	12.73 picograms per milliliter (pg/mL) Standard Deviation 18.04	8.31 picograms per milliliter (pg/mL) Standard Deviation 9.47
Serum Interleukin-6 (IL-6) Level Week 52 (n=69,32,28,30)	65.99 picograms per milliliter (pg/mL) Standard Deviation 84.92	52.70 picograms per milliliter (pg/mL) Standard Deviation 33.10	35.96 picograms per milliliter (pg/mL) Standard Deviation 149.65	10.85 picograms per milliliter (pg/mL) Standard Deviation 15.17

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Safety population. Here, 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.

Outcome measures

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=100 Participants Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper n=50 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper n=51 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Serum Soluble IL-6 Receptor (sIL-6R) Level Baseline (n=99,48,50,50)	51.34 nanograms per milliliter (ng/mL) Standard Deviation 61.98	50.82 nanograms per milliliter (ng/mL) Standard Deviation 63.51	42.07 nanograms per milliliter (ng/mL) Standard Deviation 11.32	40.37 nanograms per milliliter (ng/mL) Standard Deviation 10.84
Serum Soluble IL-6 Receptor (sIL-6R) Level Week 52 (n=73,33,33,31)	600.53 nanograms per milliliter (ng/mL) Standard Deviation 217.52	464.30 nanograms per milliliter (ng/mL) Standard Deviation 153.64	76.44 nanograms per milliliter (ng/mL) Standard Deviation 149.20	64.80 nanograms per milliliter (ng/mL) Standard Deviation 105.13

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Safety population. Here, 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.

ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm/hr. A higher rate is consistent with inflammation.

Outcome measures

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=100 Participants Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper n=50 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper n=51 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Erythrocyte Sedimentation Rate (ESR) Baseline (n=99,49,50,51)	19.00 mm/hr Inter-Quartile Range 61.98 • Interval 10.0 to 35.0	15.00 mm/hr Inter-Quartile Range 63.51 • Interval 10.0 to 30.0	23.00 mm/hr Inter-Quartile Range 11.32 • Interval 9.0 to 36.0	20.00 mm/hr Inter-Quartile Range 10.84 • Interval 8.0 to 38.0
Erythrocyte Sedimentation Rate (ESR) Week 52 (n=76,35,35,33)	3.00 mm/hr Interval 2.0 to 5.0	5.00 mm/hr Interval 2.0 to 7.0	20.00 mm/hr Interval 11.0 to 36.0	24.00 mm/hr Interval 10.0 to 37.0

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Safety population. Here, 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.

The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

Outcome measures

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=100 Participants Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper n=50 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper n=51 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
C-Reactive Protein (CRP) Level Baseline (n=100,49,50,51)	3.67 milligrams per liter (mg/L) Inter-Quartile Range 61.98 • Interval 1.02 to 9.26	4.52 milligrams per liter (mg/L) Inter-Quartile Range 63.51 • Interval 1.55 to 9.75	3.64 milligrams per liter (mg/L) Inter-Quartile Range 11.32 • Interval 1.2 to 9.59	3.56 milligrams per liter (mg/L) Inter-Quartile Range 10.84 • Interval 1.17 to 7.24
C-Reactive Protein (CRP) Level Week 52 (n=76,35,35,33)	0.30 milligrams per liter (mg/L) Interval 0.2 to 0.59	0.33 milligrams per liter (mg/L) Interval 0.2 to 0.72	4.90 milligrams per liter (mg/L) Interval 2.25 to 9.25	8.12 milligrams per liter (mg/L) Interval 2.02 to 14.4

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Safety population. Here, 'Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

All samples were tested by screening assay, and those samples that were positive were further analyzed by a confirmation assay to confirm specificity. Percentage of participants who has a positive confirmation assay result any time after the initial drug administration with a negative confirmation assay result at baseline was reported.

Outcome measures

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=95 Participants Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=46 Participants Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper n=49 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper n=47 Participants Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Percentage of Participants With Anti-Tocilizumab Antibodies	1.1 percentage of participants	6.5 percentage of participants	2.0 percentage of participants	2.1 percentage of participants

Adverse Events

Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper

Serious events: 15 serious events

Other events: 87 other events

Deaths: 0 deaths

Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper

Serious events: 7 serious events

Other events: 44 other events

Deaths: 0 deaths

Part 1: Placebo + 26 Weeks Prednisone Taper

Serious events: 11 serious events

Other events: 47 other events

Deaths: 0 deaths

Part 1: Placebo + 52 Weeks Prednisone Taper

Serious events: 13 serious events

Other events: 44 other events

Deaths: 0 deaths

Part 2: No Tocilizumab (Placebo in Part 1)

Serious events: 7 serious events

Other events: 33 other events

Deaths: 0 deaths

Part 2: No Tocilizumab (Tocilizumab in Part 1)

Serious events: 11 serious events

Other events: 50 other events

Deaths: 0 deaths

Part 2: Tocilizumab (Placebo in Part 1)

Serious events: 18 serious events

Other events: 44 other events

Deaths: 0 deaths

Part 2: Tocilizumab (Tocilizumab in Part 1)

Serious events: 23 serious events

Other events: 61 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=100 participants at risk Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=49 participants at risk Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper n=50 participants at risk Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper n=51 participants at risk Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.	Part 2: No Tocilizumab (Placebo in Part 1) n=40 participants at risk Participants did not receive tocilizumab in Part 2 from Week 52 up to Week 156. These participants received placebo during Part 1 (Weeks 1 to 52).	Part 2: No Tocilizumab (Tocilizumab in Part 1) n=58 participants at risk Participants did not receive tocilizumab in Part 2 from Week 52 up to Week 156. These participants received tocilizumab during Part 1 (Weeks 1 to 52).	Part 2: Tocilizumab (Placebo in Part 1) n=50 participants at risk Participants received open-label tocilizumab as determined by the investigator during Part 2 of the study (from Week 52 up to Week 156). These participants received placebo during Part 1 (Weeks 1 to 52).	Part 2: Tocilizumab (Tocilizumab in Part 1) n=67 participants at risk Participants received open-label tocilizumab as determined by the investigator during Part 2 of the study (from Week 52 up to Week 156). These participants received tocilizumab during Part 1 (Weeks 1 to 52).
Injury, poisoning and procedural complications Laceration	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	3.0% 2/67 • Up to 156 weeks Safety population
Eye disorders Glaucoma	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Gastritis erosive	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Stomatitis	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Erysipelas	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Pneumonia	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Injury, poisoning and procedural complications Postoperative wound complication	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Nervous system disorders Paraesthesia	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Nervous system disorders Syncope	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Respiratory, thoracic and mediastinal disorders Nasal inflammation	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Vascular disorders Hypertension	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Vascular disorders Temporal arteritis	1.0% 1/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	4.5% 3/67 • Up to 156 weeks Safety population
Cardiac disorders Aortic valve stenosis	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Cardiac disorders Cardiac failure	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Cardiac disorders Cardiac failure chronic	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Eye disorders Cataract	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Gastroenteritis	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	3.9% 2/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Genital herpes zoster	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Herpes zoster	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	3.9% 2/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Respiratory tract infection	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Investigations Hepatic enzyme increased	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Fibromyalgia	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Nervous system disorders Transient ischaemic attack	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Renal and urinary disorders Renal impairment	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Cardiac disorders Supraventricular tachycardia	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Cardiac disorders Tachyarrhythmia	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Diarrhoea	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Immune system disorders Drug hypersensitivity	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Cellulitis	1.0% 1/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Chronic sinusitis	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Pneumonia haemophilus	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Pyelonephritis	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Urinary tract infection	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Urosepsis	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Injury, poisoning and procedural complications Alcohol poisoning	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Injury, poisoning and procedural complications Tendon rupture	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Tendon pain	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Nervous system disorders Headache	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Psychiatric disorders Anxiety	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Psychiatric disorders Stress	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Vascular disorders Deep vein thrombosis	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Vascular disorders Hypertensive crisis	2.0% 2/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Immune system disorders Hypersensitivity	0.00% 0/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Cholangitis infective	0.00% 0/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian adenoma	0.00% 0/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Nervous system disorders Thrombotic stroke	0.00% 0/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Vascular disorders Dry gangrene	0.00% 0/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Blood and lymphatic system disorders Anaemia	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Blood and lymphatic system disorders Lymphocytosis	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Blood and lymphatic system disorders White blood cell disorder	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Cardiac disorders Angina pectoris	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Cardiac disorders Atrial fibrillation	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Cardiac disorders Acute myocardial infarction	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Injury, poisoning and procedural complications Cartilage injury	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Cardiac disorders Angina unstable	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Cardiac disorders Myocardial ischaemia	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Cardiac disorders Sinus node dysfunction	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Cardiac disorders Tachycardia	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Eye disorders Visual acuity reduced transiently	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Abdominal pain	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Anal haemorrhage	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Constipation	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Duodenal perforation	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Incarcerated inguinal hernia	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Large intestine polyp	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Pancreatitis acute	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
General disorders Non-cardiac chest pain	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
General disorders Chest pain	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
General disorders Impaired healing	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Hepatobiliary disorders Cholecystitis	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Device related infection	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Respiratory tract infection viral	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Injury, poisoning and procedural complications Fracture displacement	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Injury, poisoning and procedural complications Hand fracture	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Injury, poisoning and procedural complications Procedural haemorrhage	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Investigations Troponin increased	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Chondropathy	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Joint effusion	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer metastatic	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the vulva	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Nervous system disorders Cerebrovascular accident	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Nervous system disorders Carotid artery stenosis	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Nervous system disorders Cerebellar infarction	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Nervous system disorders Facial paresis	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Nervous system disorders Ischaemic stroke	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Nervous system disorders Presyncope	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Nervous system disorders Sciatica	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Nervous system disorders Visual field defect	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Psychiatric disorders Anxiety disorder	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Renal and urinary disorders Nephrolithiasis	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Renal and urinary disorders Acute kidney injury	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Surgical and medical procedures Cancer surgery	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Vascular disorders Haematoma	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	3.0% 2/67 • Up to 156 weeks Safety population
Vascular disorders Aortic aneurysm rupture	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Vascular disorders Aortic dissection	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Vascular disorders Intermittent claudication	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Vascular disorders Peripheral artery occlusion	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population

Other adverse events

Measure	Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper n=100 participants at risk Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper n=49 participants at risk Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 26 Weeks Prednisone Taper n=50 participants at risk Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.	Part 1: Placebo + 52 Weeks Prednisone Taper n=51 participants at risk Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.	Part 2: No Tocilizumab (Placebo in Part 1) n=40 participants at risk Participants did not receive tocilizumab in Part 2 from Week 52 up to Week 156. These participants received placebo during Part 1 (Weeks 1 to 52).	Part 2: No Tocilizumab (Tocilizumab in Part 1) n=58 participants at risk Participants did not receive tocilizumab in Part 2 from Week 52 up to Week 156. These participants received tocilizumab during Part 1 (Weeks 1 to 52).	Part 2: Tocilizumab (Placebo in Part 1) n=50 participants at risk Participants received open-label tocilizumab as determined by the investigator during Part 2 of the study (from Week 52 up to Week 156). These participants received placebo during Part 1 (Weeks 1 to 52).	Part 2: Tocilizumab (Tocilizumab in Part 1) n=67 participants at risk Participants received open-label tocilizumab as determined by the investigator during Part 2 of the study (from Week 52 up to Week 156). These participants received tocilizumab during Part 1 (Weeks 1 to 52).
Cardiac disorders Palpitations	2.0% 2/100 • Up to 156 weeks Safety population	4.1% 2/49 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	3.9% 2/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Ear and labyrinth disorders Vertigo	2.0% 2/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	3.0% 2/67 • Up to 156 weeks Safety population
Eye disorders Cataract	5.0% 5/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	7.8% 4/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	4.5% 3/67 • Up to 156 weeks Safety population
Eye disorders Dry eye	1.0% 1/100 • Up to 156 weeks Safety population	6.1% 3/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Abdominal pain upper	3.0% 3/100 • Up to 156 weeks Safety population	6.1% 3/49 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	7.8% 4/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Constipation	0.00% 0/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	7.8% 4/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Diarrhoea	12.0% 12/100 • Up to 156 weeks Safety population	6.1% 3/49 • Up to 156 weeks Safety population	16.0% 8/50 • Up to 156 weeks Safety population	9.8% 5/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	14.0% 7/50 • Up to 156 weeks Safety population	7.5% 5/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Dyspepsia	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Nausea	8.0% 8/100 • Up to 156 weeks Safety population	4.1% 2/49 • Up to 156 weeks Safety population	10.0% 5/50 • Up to 156 weeks Safety population	7.8% 4/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	10.0% 5/50 • Up to 156 weeks Safety population	4.5% 3/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Vomiting	2.0% 2/100 • Up to 156 weeks Safety population	4.1% 2/49 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	5.9% 3/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
General disorders Asthenia	5.0% 5/100 • Up to 156 weeks Safety population	6.1% 3/49 • Up to 156 weeks Safety population	10.0% 5/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
General disorders Fatigue	8.0% 8/100 • Up to 156 weeks Safety population	10.2% 5/49 • Up to 156 weeks Safety population	16.0% 8/50 • Up to 156 weeks Safety population	5.9% 3/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	12.0% 6/50 • Up to 156 weeks Safety population	9.0% 6/67 • Up to 156 weeks Safety population
General disorders Non-cardiac chest pain	1.0% 1/100 • Up to 156 weeks Safety population	4.1% 2/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	5.9% 3/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
General disorders Oedema peripheral	16.0% 16/100 • Up to 156 weeks Safety population	24.5% 12/49 • Up to 156 weeks Safety population	16.0% 8/50 • Up to 156 weeks Safety population	11.8% 6/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	10.0% 5/50 • Up to 156 weeks Safety population	6.0% 4/67 • Up to 156 weeks Safety population
Infections and infestations Bronchitis	8.0% 8/100 • Up to 156 weeks Safety population	8.2% 4/49 • Up to 156 weeks Safety population	10.0% 5/50 • Up to 156 weeks Safety population	9.8% 5/51 • Up to 156 weeks Safety population	10.0% 4/40 • Up to 156 weeks Safety population	15.5% 9/58 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	13.4% 9/67 • Up to 156 weeks Safety population
Infections and infestations Conjunctivitis	4.0% 4/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	4.5% 3/67 • Up to 156 weeks Safety population
Infections and infestations Cystitis	7.0% 7/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	5.9% 3/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	5.2% 3/58 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	4.5% 3/67 • Up to 156 weeks Safety population
Infections and infestations Gastroenteritis	3.0% 3/100 • Up to 156 weeks Safety population	8.2% 4/49 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	5.9% 3/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	6.0% 4/67 • Up to 156 weeks Safety population
Infections and infestations Nasopharyngitis	29.0% 29/100 • Up to 156 weeks Safety population	24.5% 12/49 • Up to 156 weeks Safety population	18.0% 9/50 • Up to 156 weeks Safety population	25.5% 13/51 • Up to 156 weeks Safety population	12.5% 5/40 • Up to 156 weeks Safety population	22.4% 13/58 • Up to 156 weeks Safety population	28.0% 14/50 • Up to 156 weeks Safety population	32.8% 22/67 • Up to 156 weeks Safety population
Infections and infestations Oral herpes	4.0% 4/100 • Up to 156 weeks Safety population	10.2% 5/49 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	3.9% 2/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	3.0% 2/67 • Up to 156 weeks Safety population
Infections and infestations Pharyngitis	4.0% 4/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	5.9% 3/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Rhinitis	6.0% 6/100 • Up to 156 weeks Safety population	8.2% 4/49 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	5.9% 3/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Sinusitis	3.0% 3/100 • Up to 156 weeks Safety population	8.2% 4/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	3.9% 2/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	9.0% 6/67 • Up to 156 weeks Safety population
Infections and infestations Upper respiratory tract infection	10.0% 10/100 • Up to 156 weeks Safety population	12.2% 6/49 • Up to 156 weeks Safety population	10.0% 5/50 • Up to 156 weeks Safety population	13.7% 7/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	14.0% 7/50 • Up to 156 weeks Safety population	3.0% 2/67 • Up to 156 weeks Safety population
Infections and infestations Urinary tract infection	10.0% 10/100 • Up to 156 weeks Safety population	8.2% 4/49 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	7.8% 4/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	6.9% 4/58 • Up to 156 weeks Safety population	20.0% 10/50 • Up to 156 weeks Safety population	14.9% 10/67 • Up to 156 weeks Safety population
Injury, poisoning and procedural complications Fall	7.0% 7/100 • Up to 156 weeks Safety population	4.1% 2/49 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	3.9% 2/51 • Up to 156 weeks Safety population	10.0% 4/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	13.4% 9/67 • Up to 156 weeks Safety population
Investigations Alanine aminotransferase increased	5.0% 5/100 • Up to 156 weeks Safety population	4.1% 2/49 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Metabolism and nutrition disorders Hypercholesterolaemia	2.0% 2/100 • Up to 156 weeks Safety population	6.1% 3/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	7.5% 5/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Arthralgia	13.0% 13/100 • Up to 156 weeks Safety population	16.3% 8/49 • Up to 156 weeks Safety population	20.0% 10/50 • Up to 156 weeks Safety population	15.7% 8/51 • Up to 156 weeks Safety population	17.5% 7/40 • Up to 156 weeks Safety population	17.2% 10/58 • Up to 156 weeks Safety population	20.0% 10/50 • Up to 156 weeks Safety population	17.9% 12/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Back pain	14.0% 14/100 • Up to 156 weeks Safety population	14.3% 7/49 • Up to 156 weeks Safety population	14.0% 7/50 • Up to 156 weeks Safety population	19.6% 10/51 • Up to 156 weeks Safety population	7.5% 3/40 • Up to 156 weeks Safety population	6.9% 4/58 • Up to 156 weeks Safety population	16.0% 8/50 • Up to 156 weeks Safety population	10.4% 7/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Bursitis	1.0% 1/100 • Up to 156 weeks Safety population	8.2% 4/49 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Muscle spasms	4.0% 4/100 • Up to 156 weeks Safety population	12.2% 6/49 • Up to 156 weeks Safety population	12.0% 6/50 • Up to 156 weeks Safety population	7.8% 4/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	10.0% 5/50 • Up to 156 weeks Safety population	9.0% 6/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Musculoskeletal pain	12.0% 12/100 • Up to 156 weeks Safety population	12.2% 6/49 • Up to 156 weeks Safety population	10.0% 5/50 • Up to 156 weeks Safety population	3.9% 2/51 • Up to 156 weeks Safety population	10.0% 4/40 • Up to 156 weeks Safety population	10.3% 6/58 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	6.0% 4/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Myalgia	9.0% 9/100 • Up to 156 weeks Safety population	8.2% 4/49 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	7.8% 4/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	3.0% 2/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Neck pain	6.0% 6/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	7.8% 4/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Osteoarthritis	7.0% 7/100 • Up to 156 weeks Safety population	4.1% 2/49 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	5.9% 3/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	12.0% 6/50 • Up to 156 weeks Safety population	9.0% 6/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Pain in extremity	8.0% 8/100 • Up to 156 weeks Safety population	10.2% 5/49 • Up to 156 weeks Safety population	10.0% 5/50 • Up to 156 weeks Safety population	9.8% 5/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	8.6% 5/58 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	10.4% 7/67 • Up to 156 weeks Safety population
Nervous system disorders Dizziness	6.0% 6/100 • Up to 156 weeks Safety population	20.4% 10/49 • Up to 156 weeks Safety population	12.0% 6/50 • Up to 156 weeks Safety population	15.7% 8/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	10.0% 5/50 • Up to 156 weeks Safety population	6.0% 4/67 • Up to 156 weeks Safety population
Nervous system disorders Headache	27.0% 27/100 • Up to 156 weeks Safety population	20.4% 10/49 • Up to 156 weeks Safety population	32.0% 16/50 • Up to 156 weeks Safety population	23.5% 12/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	13.8% 8/58 • Up to 156 weeks Safety population	16.0% 8/50 • Up to 156 weeks Safety population	9.0% 6/67 • Up to 156 weeks Safety population
Nervous system disorders Paraesthesia	4.0% 4/100 • Up to 156 weeks Safety population	4.1% 2/49 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	7.8% 4/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	7.5% 5/67 • Up to 156 weeks Safety population
Nervous system disorders Tremor	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	5.9% 3/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Psychiatric disorders Anxiety	2.0% 2/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	12.0% 6/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Psychiatric disorders Depression	3.0% 3/100 • Up to 156 weeks Safety population	4.1% 2/49 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Psychiatric disorders Insomnia	4.0% 4/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	7.8% 4/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	6.0% 4/67 • Up to 156 weeks Safety population
Psychiatric disorders Sleep disorder	1.0% 1/100 • Up to 156 weeks Safety population	6.1% 3/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Respiratory, thoracic and mediastinal disorders Cough	6.0% 6/100 • Up to 156 weeks Safety population	6.1% 3/49 • Up to 156 weeks Safety population	14.0% 7/50 • Up to 156 weeks Safety population	5.9% 3/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	6.9% 4/58 • Up to 156 weeks Safety population	14.0% 7/50 • Up to 156 weeks Safety population	6.0% 4/67 • Up to 156 weeks Safety population
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.0% 3/100 • Up to 156 weeks Safety population	6.1% 3/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	5.9% 3/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	1.0% 1/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Respiratory, thoracic and mediastinal disorders Epistaxis	3.0% 3/100 • Up to 156 weeks Safety population	2.0% 1/49 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	4.5% 3/67 • Up to 156 weeks Safety population
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.0% 7/100 • Up to 156 weeks Safety population	8.2% 4/49 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	15.7% 8/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	6.0% 4/67 • Up to 156 weeks Safety population
Skin and subcutaneous tissue disorders Alopecia	5.0% 5/100 • Up to 156 weeks Safety population	14.3% 7/49 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	9.8% 5/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	3.0% 2/67 • Up to 156 weeks Safety population
Skin and subcutaneous tissue disorders Dry skin	2.0% 2/100 • Up to 156 weeks Safety population	6.1% 3/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/100 • Up to 156 weeks Safety population	4.1% 2/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	5.9% 3/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Skin and subcutaneous tissue disorders Night sweats	1.0% 1/100 • Up to 156 weeks Safety population	6.1% 3/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	6.0% 4/67 • Up to 156 weeks Safety population
Skin and subcutaneous tissue disorders Pruritus	2.0% 2/100 • Up to 156 weeks Safety population	8.2% 4/49 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Skin and subcutaneous tissue disorders Rash	7.0% 7/100 • Up to 156 weeks Safety population	10.2% 5/49 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	3.9% 2/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	7.5% 5/67 • Up to 156 weeks Safety population
Vascular disorders Haematoma	5.0% 5/100 • Up to 156 weeks Safety population	6.1% 3/49 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	2.0% 1/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Vascular disorders Hypertension	12.0% 12/100 • Up to 156 weeks Safety population	12.2% 6/49 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	7.8% 4/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	12.1% 7/58 • Up to 156 weeks Safety population	14.0% 7/50 • Up to 156 weeks Safety population	11.9% 8/67 • Up to 156 weeks Safety population
Ear and labyrinth disorders Tinnitus	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Gastritis	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	7.5% 5/67 • Up to 156 weeks Safety population
Gastrointestinal disorders Toothache	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	3.0% 2/67 • Up to 156 weeks Safety population
General disorders Discomfort	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
General disorders Gait disturbance	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Immune system disorders Drug hypersensitivity	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	3.0% 2/67 • Up to 156 weeks Safety population
Infections and infestations Herpes zoster	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	6.9% 4/58 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	3.0% 2/67 • Up to 156 weeks Safety population
Infections and infestations Influenza	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Infections and infestations Lower respiratory tract infection	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Infections and infestations Respiratory tract infection	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	10.0% 4/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	6.0% 4/67 • Up to 156 weeks Safety population
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	6.0% 4/67 • Up to 156 weeks Safety population
Injury, poisoning and procedural complications Limb injury	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	4.5% 3/67 • Up to 156 weeks Safety population
Investigations Complement factor C3 decreased	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	8.0% 4/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Investigations Complement factor C4 decreased	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Osteopenia	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	5.2% 3/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	10.0% 5/50 • Up to 156 weeks Safety population	4.5% 3/67 • Up to 156 weeks Safety population
Nervous system disorders Carpal tunnel syndrome	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	4.5% 3/67 • Up to 156 weeks Safety population
Nervous system disorders Sciatica	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	3.4% 2/58 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	7.5% 5/67 • Up to 156 weeks Safety population
Nervous system disorders Syncope	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	0.00% 0/58 • Up to 156 weeks Safety population	6.0% 3/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	5.0% 2/40 • Up to 156 weeks Safety population	1.7% 1/58 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	0.00% 0/40 • Up to 156 weeks Safety population	5.2% 3/58 • Up to 156 weeks Safety population	2.0% 1/50 • Up to 156 weeks Safety population	0.00% 0/67 • Up to 156 weeks Safety population
Skin and subcutaneous tissue disorders Eczema	0.00% 0/100 • Up to 156 weeks Safety population	0.00% 0/49 • Up to 156 weeks Safety population	0.00% 0/50 • Up to 156 weeks Safety population	0.00% 0/51 • Up to 156 weeks Safety population	2.5% 1/40 • Up to 156 weeks Safety population	5.2% 3/58 • Up to 156 weeks Safety population	4.0% 2/50 • Up to 156 weeks Safety population	1.5% 1/67 • Up to 156 weeks Safety population

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER