Trial Outcomes & Findings for Safety, Tolerability and Efficacy on Low Density Lipoprotein Cholesterol (LDL-C) of Evolocumab in Participants With Human Immunodeficiency Virus (HIV) and Hyperlipidemia/Mixed Dyslipidemia (NCT NCT02833844)

Last Updated: 2022-07-22

Results Overview

Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

467 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2022-07-22

Participant Flow

This study was conducted at 72 centers in Australia, Belgium, Brazil, Canada, France, Greece, Italy, Poland, Portugal, Romania, South Africa, Spain, Switzerland, United Kingdom, and United States. The first participant was enrolled on 22 May 2017, and the last participant was enrolled on 23 January 2019.

Participants were randomized in a 2:1 ratio to evolocumab or placebo, respectively, in a double-blind manner. Randomization was stratified by entry statin treatment and hepatitis C status.

Participant milestones

Participant milestones
Measure	Double-Blind Placebo/Open-Label Evolocumab Double-blind placebo subcutaneous (SC) injection every 4 weeks (QM) for 24 weeks in the double-blind period, followed by open-label evolocumab 420 mg SC QM for 24 weeks in the open-label period.	Double-Blind Evolocumab/Open-Label Evolocumab Double-blind evolocumab SC injection QM for 24 weeks in the double-blind period, followed by open-label evolocumab 420 mg SC QM for 24 weeks in the open-label period.
Double-Blind Period STARTED	157	310
Double-Blind Period Randomized and Treated	157	307
Double-Blind Period COMPLETED	155	303
Double-Blind Period NOT COMPLETED	2	7
Open-Label Period STARTED	152	303
Open-Label Period Received Open-Label Study Drug	152	299
Open-Label Period COMPLETED	150	301
Open-Label Period NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Double-Blind Placebo/Open-Label Evolocumab Double-blind placebo subcutaneous (SC) injection every 4 weeks (QM) for 24 weeks in the double-blind period, followed by open-label evolocumab 420 mg SC QM for 24 weeks in the open-label period.	Double-Blind Evolocumab/Open-Label Evolocumab Double-blind evolocumab SC injection QM for 24 weeks in the double-blind period, followed by open-label evolocumab 420 mg SC QM for 24 weeks in the open-label period.
Double-Blind Period Withdrawal by Subject	2	3
Double-Blind Period Protocol Violation	0	4
Open-Label Period Death	0	2
Open-Label Period Lost to Follow-up	1	0
Open-Label Period Withdrawal by Subject	1	0

Baseline Characteristics

participants with a baseline assessment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Double-Blind Placebo n=157 Participants Double-blind placebo SC injection QM for 24 weeks in the double-blind period.	Double-Blind Evolocumab n=310 Participants Double-blind evolocumab SC injection QM for 24 weeks in the double-blind period.	Total n=467 Participants Total of all reporting groups
Age, Continuous	56.2 years STANDARD_DEVIATION 8.0 • n=157 Participants	56.5 years STANDARD_DEVIATION 9.1 • n=310 Participants	56.4 years STANDARD_DEVIATION 8.7 • n=467 Participants
Sex: Female, Male Female	37 Participants n=157 Participants	45 Participants n=310 Participants	82 Participants n=467 Participants
Sex: Female, Male Male	120 Participants n=157 Participants	265 Participants n=310 Participants	385 Participants n=467 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	21 Participants n=157 Participants	41 Participants n=310 Participants	62 Participants n=467 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	136 Participants n=157 Participants	269 Participants n=310 Participants	405 Participants n=467 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=157 Participants	0 Participants n=310 Participants	0 Participants n=467 Participants
Race/Ethnicity, Customized Asian	3 Participants n=157 Participants	3 Participants n=310 Participants	6 Participants n=467 Participants
Race/Ethnicity, Customized Black or African American	25 Participants n=157 Participants	54 Participants n=310 Participants	79 Participants n=467 Participants
Race/Ethnicity, Customized White	125 Participants n=157 Participants	246 Participants n=310 Participants	371 Participants n=467 Participants
Race/Ethnicity, Customized Multiple Races	1 Participants n=157 Participants	0 Participants n=310 Participants	1 Participants n=467 Participants
Race/Ethnicity, Customized Other, Not Specified	3 Participants n=157 Participants	7 Participants n=310 Participants	10 Participants n=467 Participants
Stratification Factor: Statin Use at Baseline Statin Use = Yes	128 Participants n=157 Participants	256 Participants n=310 Participants	384 Participants n=467 Participants
Stratification Factor: Statin Use at Baseline Statin Use = No	29 Participants n=157 Participants	54 Participants n=310 Participants	83 Participants n=467 Participants
Stratification Factor: Hepatitis C Virus (HCV) Status at Baseline HCV = Yes	7 Participants n=157 Participants	10 Participants n=310 Participants	17 Participants n=467 Participants
Stratification Factor: Hepatitis C Virus (HCV) Status at Baseline HCV= No	150 Participants n=157 Participants	300 Participants n=310 Participants	450 Participants n=467 Participants
Low-Density Lipoprotein Cholesterol (LDL-C)	133.26 mg/dL STANDARD_DEVIATION 39.97 • n=157 Participants • participants with a baseline assessment	133.25 mg/dL STANDARD_DEVIATION 40.25 • n=306 Participants • participants with a baseline assessment	133.25 mg/dL STANDARD_DEVIATION 40.11 • n=463 Participants • participants with a baseline assessment

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: randomized participants who received at least 1 dose of investigational product. Participants with an assessment.

Outcome measures

Outcome measures
Measure	Double-Blind Placebo n=151 Participants Double-blind placebo SC injection QM for 24 weeks.	Double-Blind Evolocumab n=295 Participants Double-blind evolocumab SC injection QM for 24 weeks.
Percent Change From Baseline in LDL-C at Week 24	1.68 percent change Standard Error 2.03	-55.23 percent change Standard Error 1.52

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: randomized participants who received at least 1 dose of investigational product. Participants with an assessment.

Outcome measures

Outcome measures
Measure	Double-Blind Placebo n=151 Participants Double-blind placebo SC injection QM for 24 weeks.	Double-Blind Evolocumab n=295 Participants Double-blind evolocumab SC injection QM for 24 weeks.
Change From Baseline in LDL-C at Week 24	-2.3 mg/dL Standard Error 3.1	-77.5 mg/dL Standard Error 2.3

SECONDARY outcome

Timeframe: Week 24

Population: Full Analysis Set: randomized participants who received at least 1 dose of investigational product. Participants with observed data.

Outcome measures

Outcome measures
Measure	Double-Blind Placebo n=151 Participants Double-blind placebo SC injection QM for 24 weeks.	Double-Blind Evolocumab n=296 Participants Double-blind evolocumab SC injection QM for 24 weeks.
Percentage of Participants Acheiving LDL-C < 70 mg/dL (1.8 mmol/L) at Week 24	7.9 percentage of participants Interval 4.6 to 13.4	73.3 percentage of participants Interval 68.0 to 78.0

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: randomized participants who received at least 1 dose of investigational product. Participants with observed data.

Outcome measures

Outcome measures
Measure	Double-Blind Placebo n=151 Participants Double-blind placebo SC injection QM for 24 weeks.	Double-Blind Evolocumab n=295 Participants Double-blind evolocumab SC injection QM for 24 weeks.
Percentage of Participants With an LDL-C Response (50% Reduction of LDL-C From Baseline) at Week 24	0.7 percentage of participants Interval 0.1 to 3.7	72.5 percentage of participants Interval 67.2 to 77.3

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: randomized participants who received at least 1 dose of investigational product. Participants with an assessment.

Outcome measures

Outcome measures
Measure	Double-Blind Placebo n=152 Participants Double-blind placebo SC injection QM for 24 weeks.	Double-Blind Evolocumab n=296 Participants Double-blind evolocumab SC injection QM for 24 weeks.
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (HDL-C) at Week 24	2.86 percent change Standard Error 1.74	-48.07 percent change Standard Error 1.31

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: randomized participants who received at least 1 dose of investigational product. Participants with an assessment.

Outcome measures

Outcome measures
Measure	Double-Blind Placebo n=153 Participants Double-blind placebo SC injection QM for 24 weeks.	Double-Blind Evolocumab n=302 Participants Double-blind evolocumab SC injection QM for 24 weeks.
Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 24	2.59 percent change Standard Error 1.50	-45.14 percent change Standard Error 1.13

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: randomized participants who received at least 1 dose of investigational product. Participants with an assessment.

Outcome measures

Outcome measures
Measure	Double-Blind Placebo n=152 Participants Double-blind placebo SC injection QM for 24 weeks.	Double-Blind Evolocumab n=296 Participants Double-blind evolocumab SC injection QM for 24 weeks.
Percent Change From Baseline in Total Cholesterol (TC) at Week 24	2.34 percent change Standard Error 1.40	-35.78 percent change Standard Error 1.06

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: randomized participants who received at least 1 dose of investigational product. Participants with an assessment.

Outcome measures

Outcome measures
Measure	Double-Blind Placebo n=153 Participants Double-blind placebo SC injection QM for 24 weeks.	Double-Blind Evolocumab n=302 Participants Double-blind evolocumab SC injection QM for 24 weeks.
Percent Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 24	10.35 percent change Standard Error 3.34	-16.44 percent change Standard Error 2.57

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: randomized participants who received at least 1 dose of investigational product. Participants with an assessment.

Outcome measures

Outcome measures
Measure	Double-Blind Placebo n=152 Participants Double-blind placebo SC injection QM for 24 weeks.	Double-Blind Evolocumab n=296 Participants Double-blind evolocumab SC injection QM for 24 weeks.
Percent Change From Baseline in Triglycerides at Week 24	13.21 percent change Standard Error 3.80	-9.25 percent change Standard Error 2.89

SECONDARY outcome

Timeframe: Bseline, Week 24

Population: Full Analysis Set: randomized participants who received at least 1 dose of investigational product. Participants with an assessment.

Outcome measures

Outcome measures
Measure	Double-Blind Placebo n=152 Participants Double-blind placebo SC injection QM for 24 weeks.	Double-Blind Evolocumab n=296 Participants Double-blind evolocumab SC injection QM for 24 weeks.
Percent Change From Baseline in HDL-C at Week 24	2.73 percent change Standard Error 1.57	11.08 percent change Standard Error 1.20

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: randomized participants who received at least 1 dose of investigational product. Participants with an assessment.

Outcome measures

Outcome measures
Measure	Double-Blind Placebo n=141 Participants Double-blind placebo SC injection QM for 24 weeks.	Double-Blind Evolocumab n=284 Participants Double-blind evolocumab SC injection QM for 24 weeks.
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 24	12.34 percent change Standard Error 3.54	-9.81 percent change Standard Error 2.65

Adverse Events

Double-Blind Placebo

Serious events: 8 serious events

Other events: 41 other events

Deaths: 0 deaths

Double-Blind Evolocumab

Serious events: 10 serious events

Other events: 78 other events

Deaths: 0 deaths

Double-Blind Placebo/Open-Label Evolocumab

Serious events: 8 serious events

Other events: 23 other events

Deaths: 0 deaths

Double-Blind Evolocumab/Open-Label Evolocumab

Serious events: 14 serious events

Other events: 50 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Double-Blind Placebo n=157 participants at risk Double-blind placebo SC injection QM for 24 weeks.	Double-Blind Evolocumab n=307 participants at risk Double-blind evolocumab SC injection QM for 24 weeks.	Double-Blind Placebo/Open-Label Evolocumab n=152 participants at risk Participants originally randomized to placebo in the double-blind period then received open-label evolocumab 420 mg SC QM for 24 weeks.	Double-Blind Evolocumab/Open-Label Evolocumab n=299 participants at risk Participants originally randomized to evolocumab in the double-blind period then received open-label evolocumab 420 mg SC QM for 24 weeks.
Cardiac disorders Angina pectoris	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Cardiac disorders Atrial fibrillation	0.64% 1/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.66% 1/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Cardiac disorders Cardiac failure congestive	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Cardiac disorders Coronary artery stenosis	0.64% 1/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Cardiac disorders Myocardial ischaemia	0.64% 1/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Cardiac disorders Ventricular tachycardia	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Gastrointestinal disorders Anal fistula	0.64% 1/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Gastrointestinal disorders Vomiting	0.64% 1/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Hepatobiliary disorders Cholecystitis acute	0.64% 1/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Infections and infestations Staphylococcal infection	0.64% 1/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Infections and infestations Tracheobronchitis	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.64% 1/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.3% 2/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.64% 1/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.66% 1/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Nervous system disorders Cerebrovascular accident	0.64% 1/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Nervous system disorders Migraine	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Psychiatric disorders Depression	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Vascular disorders Hypertensive emergency	0.64% 1/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Blood and lymphatic system disorders Blood loss anaemia	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.66% 1/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Cardiac disorders Angina unstable	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Cardiac disorders Pericarditis constrictive	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Gastrointestinal disorders Gastric ulcer	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.66% 1/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.66% 1/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
General disorders Non-cardiac chest pain	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Immune system disorders Anaphylactic reaction	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Infections and infestations Gastroenteritis bacterial	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Infections and infestations Helicobacter gastritis	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.66% 1/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Infections and infestations Pneumonia	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Infections and infestations Respiratory syncytial virus bronchitis	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Injury, poisoning and procedural complications Brain contusion	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.66% 1/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.66% 1/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.

Other adverse events
Measure	Double-Blind Placebo n=157 participants at risk Double-blind placebo SC injection QM for 24 weeks.	Double-Blind Evolocumab n=307 participants at risk Double-blind evolocumab SC injection QM for 24 weeks.	Double-Blind Placebo/Open-Label Evolocumab n=152 participants at risk Participants originally randomized to placebo in the double-blind period then received open-label evolocumab 420 mg SC QM for 24 weeks.	Double-Blind Evolocumab/Open-Label Evolocumab n=299 participants at risk Participants originally randomized to evolocumab in the double-blind period then received open-label evolocumab 420 mg SC QM for 24 weeks.
Gastrointestinal disorders Abdominal pain	2.5% 4/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.98% 3/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Gastrointestinal disorders Diarrhoea	4.5% 7/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	3.6% 11/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.66% 1/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	2.7% 8/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
General disorders Chest pain	3.2% 5/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.65% 2/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
General disorders Influenza like illness	2.5% 4/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	3.9% 12/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	1.3% 2/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	1.0% 3/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Infections and infestations Nasopharyngitis	1.3% 2/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	3.3% 10/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	3.9% 6/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	3.0% 9/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Infections and infestations Upper respiratory tract infection	2.5% 4/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	2.3% 7/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.66% 1/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	1.7% 5/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Musculoskeletal and connective tissue disorders Arthralgia	1.9% 3/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	2.9% 9/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.66% 1/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	1.7% 5/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Musculoskeletal and connective tissue disorders Back pain	2.5% 4/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	3.9% 12/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	2.6% 4/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.67% 2/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Musculoskeletal and connective tissue disorders Myalgia	3.8% 6/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	2.0% 6/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	1.0% 3/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Musculoskeletal and connective tissue disorders Pain in extremity	1.9% 3/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	2.3% 7/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Nervous system disorders Headache	3.2% 5/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	2.0% 6/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	2.0% 3/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Nervous system disorders Paraesthesia	0.00% 0/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	2.3% 7/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Vascular disorders Hypertension	3.2% 5/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.00% 0/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	2.0% 3/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	1.3% 4/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Infections and infestations Bronchitis	1.9% 3/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	1.6% 5/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	1.3% 2/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	2.3% 7/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.
Infections and infestations Sinusitis	0.64% 1/157 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.33% 1/307 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	0.66% 1/152 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.	2.7% 8/299 • Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All-cause mortality is reported for all participants randomized in the DBT Period as well as for all participants who entered into the OLE Period.