Trial Outcomes & Findings for Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-4 (NCT NCT02634580)

NCT ID: NCT02634580

Last Updated: 2020-11-10

Results Overview

For all efficacy endpoints the two dosing regimens (every 2 weeks and every month) for each treatment were pooled for analysis.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 61 participants
• Primary outcome timeframe: Baseline and Weeks 10 and 12
• Results posted on: 2020-11-10

Participant Flow

This study was conducted at 30 centers in Japan. Participants were enrolled from 27 February 2016 to 18 May 2017. The study consisted of a 12-week double-blind (DB) treatment period and a 9-month open-label extension (OLE) period.

Participants were randomized 1:1:2:2 into 1 of 4 treatment groups for the 12-week, double-blind treatment period. Randomization was stratified by screening low-density lipoprotein cholesterol (LDL-C) level (< 180 mg/dL vs. ≥ 180 mg/dL) and baseline statin use (yes vs. no).

Participant milestones

Measure	Ezetimibe (Q2W) Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for 12 weeks in the double-blind treatment period. From week 12 to week 48 participants self-administered 140 mg evolocumab subcutaneously every 2 weeks in the open-label extension period.	Ezetimibe (QM) Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for 12 weeks in the double-blind treatment period. From week 12 to week 48 participants self-administered 420 mg evolocumab subcutaneously once a month in the open-label extension period.	Evolocumab Q2W Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for 12 weeks in the double-blind treatment period. From week 12 to week 48 participants self-administered 140 mg evolocumab subcutaneously every 2 weeks in the open-label extension period.	Evolocumab QM Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for 12 weeks in the double-blind treatment period. From week 12 to week 48 participants self-administered 420 mg evolocumab subcutaneously once a month in the open-label extension period.
Double-blind Treatment Period STARTED	10	11	19	21
Double-blind Treatment Period COMPLETED	9	11	18	20
Double-blind Treatment Period NOT COMPLETED	1	0	1	1
Open-label Extension Period STARTED	9	11	18	21
Open-label Extension Period Received Open-label Treatment	9	11	18	20
Open-label Extension Period COMPLETED	9	10	18	20
Open-label Extension Period NOT COMPLETED	0	1	0	1

Reasons for withdrawal

Measure	Ezetimibe (Q2W) Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for 12 weeks in the double-blind treatment period. From week 12 to week 48 participants self-administered 140 mg evolocumab subcutaneously every 2 weeks in the open-label extension period.	Ezetimibe (QM) Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for 12 weeks in the double-blind treatment period. From week 12 to week 48 participants self-administered 420 mg evolocumab subcutaneously once a month in the open-label extension period.	Evolocumab Q2W Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for 12 weeks in the double-blind treatment period. From week 12 to week 48 participants self-administered 140 mg evolocumab subcutaneously every 2 weeks in the open-label extension period.	Evolocumab QM Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for 12 weeks in the double-blind treatment period. From week 12 to week 48 participants self-administered 420 mg evolocumab subcutaneously once a month in the open-label extension period.
Double-blind Treatment Period Subject Request	1	0	1	1
Open-label Extension Period Withdrawal by Subject	0	1	0	1

Baseline Characteristics

Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-4

Baseline characteristics by cohort

Measure	Ezetimibe (Q2W) n=10 Participants Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for 12 weeks.	Ezetimibe (QM) n=11 Participants Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab Q2W n=19 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for 12 weeks.	Evolocumab QM n=21 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for 12 weeks.	Total n=61 Participants Total of all reporting groups
Age, Continuous	65.2 years STANDARD_DEVIATION 10.8 • n=93 Participants	58.7 years STANDARD_DEVIATION 12.5 • n=4 Participants	65.1 years STANDARD_DEVIATION 10.5 • n=27 Participants	66.4 years STANDARD_DEVIATION 9.3 • n=483 Participants	64.4 years STANDARD_DEVIATION 10.6 • n=36 Participants
Sex: Female, Male Female	5 Participants n=93 Participants	5 Participants n=4 Participants	9 Participants n=27 Participants	12 Participants n=483 Participants	31 Participants n=36 Participants
Sex: Female, Male Male	5 Participants n=93 Participants	6 Participants n=4 Participants	10 Participants n=27 Participants	9 Participants n=483 Participants	30 Participants n=36 Participants
Race/Ethnicity, Customized Japanese	10 Participants n=93 Participants	11 Participants n=4 Participants	19 Participants n=27 Participants	21 Participants n=483 Participants	61 Participants n=36 Participants
Intolerance to Statins One statin	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	2 Participants n=36 Participants
Intolerance to Statins Two statins	7 Participants n=93 Participants	10 Participants n=4 Participants	14 Participants n=27 Participants	14 Participants n=483 Participants	45 Participants n=36 Participants
Intolerance to Statins Three statins	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants	4 Participants n=483 Participants	10 Participants n=36 Participants
Intolerance to Statins Four or more statins	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	3 Participants n=483 Participants	4 Participants n=36 Participants
Stratification Factor: Screening LDL-C Level < 180 mg/dL [4.66 mmol/L]	5 Participants n=93 Participants	6 Participants n=4 Participants	9 Participants n=27 Participants	10 Participants n=483 Participants	30 Participants n=36 Participants
Stratification Factor: Screening LDL-C Level ≥ 180 mg/dL [4.66 mmol/L]	5 Participants n=93 Participants	5 Participants n=4 Participants	10 Participants n=27 Participants	11 Participants n=483 Participants	31 Participants n=36 Participants
Stratification Factor: Baseline Statin Use Yes	3 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants	5 Participants n=483 Participants	14 Participants n=36 Participants
Stratification Factor: Baseline Statin Use No	7 Participants n=93 Participants	8 Participants n=4 Participants	16 Participants n=27 Participants	16 Participants n=483 Participants	47 Participants n=36 Participants
LDL-C Concentration	181.0 mg/dL STANDARD_DEVIATION 34.7 • n=93 Participants	182.7 mg/dL STANDARD_DEVIATION 72.2 • n=4 Participants	198.1 mg/dL STANDARD_DEVIATION 64.1 • n=27 Participants	188.0 mg/dL STANDARD_DEVIATION 41.6 • n=483 Participants	189.0 mg/dL STANDARD_DEVIATION 53.9 • n=36 Participants
Total Cholesterol Concentration	280.0 mg/dL STANDARD_DEVIATION 34.4 • n=93 Participants	275.2 mg/dL STANDARD_DEVIATION 79.7 • n=4 Participants	282.0 mg/dL STANDARD_DEVIATION 63.9 • n=27 Participants	282.3 mg/dL STANDARD_DEVIATION 49.6 • n=483 Participants	280.5 mg/dL STANDARD_DEVIATION 57.3 • n=36 Participants
High-density Lipoprotein Cholesterol (HDL-C) Concentration	62.5 mg/dL STANDARD_DEVIATION 15.6 • n=93 Participants	64.1 mg/dL STANDARD_DEVIATION 16.1 • n=4 Participants	54.3 mg/dL STANDARD_DEVIATION 18.2 • n=27 Participants	64.1 mg/dL STANDARD_DEVIATION 20.9 • n=483 Participants	60.8 mg/dL STANDARD_DEVIATION 18.6 • n=36 Participants
Very Low-density Lipoprotein Cholesterol (VLDL) Concentration	36.5 mg/dL STANDARD_DEVIATION 21.9 • n=93 Participants	28.4 mg/dL STANDARD_DEVIATION 16.1 • n=4 Participants	29.6 mg/dL STANDARD_DEVIATION 12.0 • n=27 Participants	30.2 mg/dL STANDARD_DEVIATION 12.3 • n=483 Participants	30.7 mg/dL STANDARD_DEVIATION 14.7 • n=36 Participants
Triglycerides Concentration	183.1 mg/dL STANDARD_DEVIATION 111.1 • n=93 Participants	142.3 mg/dL STANDARD_DEVIATION 80.1 • n=4 Participants	148.0 mg/dL STANDARD_DEVIATION 59.8 • n=27 Participants	151.0 mg/dL STANDARD_DEVIATION 61.3 • n=483 Participants	153.8 mg/dL STANDARD_DEVIATION 73.7 • n=36 Participants
Apolipoprotein B Concentration	132.1 mg/dL STANDARD_DEVIATION 19.4 • n=93 Participants	121.9 mg/dL STANDARD_DEVIATION 29.3 • n=4 Participants	140.4 mg/dL STANDARD_DEVIATION 31.7 • n=27 Participants	138.7 mg/dL STANDARD_DEVIATION 26.2 • n=483 Participants	135.1 mg/dL STANDARD_DEVIATION 27.9 • n=36 Participants
Non-HDL-C Concentration	217.5 mg/dL STANDARD_DEVIATION 37.3 • n=93 Participants	211.1 mg/dL STANDARD_DEVIATION 71.2 • n=4 Participants	227.7 mg/dL STANDARD_DEVIATION 63.3 • n=27 Participants	218.2 mg/dL STANDARD_DEVIATION 42.2 • n=483 Participants	219.8 mg/dL STANDARD_DEVIATION 53.7 • n=36 Participants
Total cholesterol/HDL-C ratio	4.8 ratio STANDARD_DEVIATION 1.4 • n=93 Participants	4.4 ratio STANDARD_DEVIATION 1.1 • n=4 Participants	5.7 ratio STANDARD_DEVIATION 2.0 • n=27 Participants	4.8 ratio STANDARD_DEVIATION 1.4 • n=483 Participants	5.0 ratio STANDARD_DEVIATION 1.6 • n=36 Participants
ApolipoproteinB/Apolipoprotein A1 Ratio	0.8 ratio STANDARD_DEVIATION 0.2 • n=93 Participants	0.8 ratio STANDARD_DEVIATION 0.2 • n=4 Participants	1.0 ratio STANDARD_DEVIATION 0.4 • n=27 Participants	0.9 ratio STANDARD_DEVIATION 0.2 • n=483 Participants	0.9 ratio STANDARD_DEVIATION 0.3 • n=36 Participants
Lipoprotein(a) Concentration	48.0 nmol/L STANDARD_DEVIATION 72.3 • n=93 Participants	66.0 nmol/L STANDARD_DEVIATION 83.2 • n=4 Participants	61.3 nmol/L STANDARD_DEVIATION 72.6 • n=27 Participants	66.2 nmol/L STANDARD_DEVIATION 91.0 • n=483 Participants	61.7 nmol/L STANDARD_DEVIATION 79.5 • n=36 Participants

PRIMARY outcome

Timeframe: Baseline and Weeks 10 and 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

For all efficacy endpoints the two dosing regimens (every 2 weeks and every month) for each treatment were pooled for analysis.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12	-20.39 percent change Standard Error 3.19	-59.75 percent change Standard Error 2.30

PRIMARY outcome

Timeframe: Baseline and week 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12	-19.13 percent change Standard Error 3.45	-59.27 percent change Standard Error 2.50

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Change From Baseline in LDL-C at the Mean of Weeks 10 and 12	-35.6 mg/dL Standard Error 6.6	-113.2 mg/dL Standard Error 4.8

SECONDARY outcome

Timeframe: Baseline and week 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Change From Baseline in LDL-C at Week 12	-33.4 mg/dL Standard Error 7.0	-112.7 mg/dL Standard Error 5.1

SECONDARY outcome

Timeframe: Weeks 10 and 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Mean low density lipoprotein-cholesterol response was defined as LDL-C < 70 mg/dL [1.8 mol/L].

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL	0.00 percentage of participants Interval 0.0 to 16.11	56.41 percentage of participants Interval 40.98 to 70.7

SECONDARY outcome

Timeframe: Week 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percentage of Participants Who Achieved a LDL-C of Less Than 70 mg/dL at Week 12	0.00 percentage of participants Interval 0.0 to 16.11	52.63 percentage of participants Interval 37.26 to 67.52

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12	-13.80 percent change Standard Error 2.17	-39.24 percent change Standard Error 1.57

SECONDARY outcome

Timeframe: Baseline and week 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in Total Cholesterol at Week 12	-12.69 percent change Standard Error 2.34	-38.52 percent change Standard Error 1.70

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12	-18.82 percent change Standard Error 2.77	-52.35 percent change Standard Error 2.01

SECONDARY outcome

Timeframe: Baseline and week 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in Non-HDL-C at Week 12	-18.28 percent change Standard Error 3.03	-51.71 percent change Standard Error 2.20

SECONDARY outcome

Timeframe: Baseline and Weeks 10 and 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12	-13.23 percent change Standard Error 2.69	-48.90 percent change Standard Error 1.93

SECONDARY outcome

Timeframe: Baseline and week 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in Apolipoprotein B at Week 12	-11.32 percent change Standard Error 2.99	-47.91 percent change Standard Error 2.14

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12	-15.73 percent change Standard Error 2.69	-44.34 percent change Standard Error 1.94

SECONDARY outcome

Timeframe: Baseline and week 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12	-17.34 percent change Standard Error 2.81	-44.39 percent change Standard Error 2.04

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12	-15.39 percent change Standard Error 2.67	-52.46 percent change Standard Error 1.91

SECONDARY outcome

Timeframe: Baseline and week 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12	-15.62 percent change Standard Error 2.88	-51.91 percent change Standard Error 2.06

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12	-5.89 percent change Standard Error 4.34	-37.02 percent change Standard Error 3.11

SECONDARY outcome

Timeframe: Baseline and week 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in Lipoprotein(a) at Week 12	-5.21 percent change Standard Error 5.02	-36.41 percent change Standard Error 3.59

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12	-5.21 percent change Standard Error 5.92	-1.73 percent change Standard Error 4.28

SECONDARY outcome

Timeframe: Baseline and week 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in Triglycerides at Week 12	-9.87 percent change Standard Error 7.71	1.92 percent change Standard Error 5.60

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12	3.10 percent change Standard Error 2.50	11.06 percent change Standard Error 1.80

SECONDARY outcome

Timeframe: Baseline and week 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in HDL-C at Week 12	6.45 percent change Standard Error 2.59	12.04 percent change Standard Error 1.88

SECONDARY outcome

Timeframe: Baseline and weeks 10 and 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12	-4.67 percent change Standard Error 5.89	-5.34 percent change Standard Error 4.25

SECONDARY outcome

Timeframe: Baseline and week 12

Population: All randomized participants who received at least 1 dose of study drug in the double-blind treatment period.

Outcome measures

Measure	Ezetimibe n=21 Participants Participants received placebo subcutaneous injection once every 2 weeks or once a month and 10 mg ezetimibe orally once a day for 12 weeks.	Evolocumab n=40 Participants Participants received SC evolocumab 140 mg once every 2 weeks or 420 mg once a month and placebo tablets once a day for 12 weeks.
Percent Change From Baseline in VLDL-C at Week 12	-9.06 percent change Standard Error 8.00	-1.42 percent change Standard Error 5.80

Adverse Events

DB Period: Ezetimibe (Q2W)

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

DB Period: Ezetimibe (QM)

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

DB Period: Evolocumab Q2W

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

DB Period: Evolocumab QM

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

OLE Period: Evolocumab

Serious events: 4 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Measure	DB Period: Ezetimibe (Q2W) n=10 participants at risk Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for 12 weeks.	DB Period: Ezetimibe (QM) n=11 participants at risk Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for 12 weeks.	DB Period: Evolocumab Q2W n=19 participants at risk Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for 12 weeks.	DB Period: Evolocumab QM n=21 participants at risk Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for 12 weeks.	OLE Period: Evolocumab n=58 participants at risk Participants received evolocumab by subcutaneous injection from week 12 to week 48 at the same dosing interval as the investigational product regimen that they were randomized to during the double-blind period (ie, every 2 weeks or once monthly) during the open-label extension (OLE) period.
Cardiac disorders Acute myocardial infarction	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Musculoskeletal and connective tissue disorders Osteoarthritis	10.0% 1/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Cardiac disorders Myocardial ischaemia	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
General disorders Mass	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Nervous system disorders Transient ischaemic attack	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.

Other adverse events

Measure	DB Period: Ezetimibe (Q2W) n=10 participants at risk Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for 12 weeks.	DB Period: Ezetimibe (QM) n=11 participants at risk Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for 12 weeks.	DB Period: Evolocumab Q2W n=19 participants at risk Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for 12 weeks.	DB Period: Evolocumab QM n=21 participants at risk Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for 12 weeks.	OLE Period: Evolocumab n=58 participants at risk Participants received evolocumab by subcutaneous injection from week 12 to week 48 at the same dosing interval as the investigational product regimen that they were randomized to during the double-blind period (ie, every 2 weeks or once monthly) during the open-label extension (OLE) period.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	4.8% 1/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Gastrointestinal disorders Abdominal distension	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	10.5% 2/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Gastrointestinal disorders Abdominal pain	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	5.3% 1/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	5.3% 1/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Gastrointestinal disorders Constipation	10.0% 1/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	5.3% 1/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	3.4% 2/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Gastrointestinal disorders Diarrhoea	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	18.2% 2/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	5.3% 1/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	4.8% 1/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	5.2% 3/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	5.3% 1/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Gastrointestinal disorders Oral mucosa haematoma	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	4.8% 1/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Gastrointestinal disorders Tooth loss	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	4.8% 1/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
General disorders Chest discomfort	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
General disorders Injection site bruising	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	4.8% 1/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
General disorders Injection site erythema	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
General disorders Injection site pain	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.5% 2/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
General disorders Injection site reaction	10.0% 1/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
General disorders Injection site swelling	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
General disorders Pyrexia	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Infections and infestations Bronchitis	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	4.8% 1/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Infections and infestations Cystitis	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	4.8% 1/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Infections and infestations Nasopharyngitis	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	23.8% 5/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	29.3% 17/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Infections and infestations Pharyngitis	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	15.8% 3/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	4.8% 1/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	3.4% 2/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Infections and infestations Tonsillitis	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	4.8% 1/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	4.8% 1/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	4.8% 1/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Investigations Blood creatine phosphokinase increased	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	5.3% 1/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	3.4% 2/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	4.8% 1/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	5.3% 1/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	4.8% 1/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Musculoskeletal and connective tissue disorders Myositis	10.0% 1/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	5.3% 1/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Musculoskeletal and connective tissue disorders Plantar fasciitis	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	5.3% 1/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Musculoskeletal and connective tissue disorders Synovial cyst	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Musculoskeletal and connective tissue disorders Tenosynovitis	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	5.3% 1/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Nervous system disorders Dizziness	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Nervous system disorders Headache	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	5.3% 1/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Respiratory, thoracic and mediastinal disorders Cough	10.0% 1/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	5.3% 1/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	4.8% 1/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	3.4% 2/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Skin and subcutaneous tissue disorders Miliaria	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	5.3% 1/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	1.7% 1/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Skin and subcutaneous tissue disorders Onychomalacia	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	4.8% 1/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	5.3% 1/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	3.4% 2/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	4.8% 1/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Vascular disorders Hypertension	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.5% 2/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	5.2% 3/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Vascular disorders Varicose vein	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	9.1% 1/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Cardiac disorders Coronary artery stenosis	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	3.4% 2/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	3.4% 2/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Infections and infestations Gastroenteritis	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	3.4% 2/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Infections and infestations Influenza	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	3.4% 2/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	3.4% 2/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	3.4% 2/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	6.9% 4/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	3.4% 2/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	3.4% 2/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Nervous system disorders Intercostal neuralgia	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	3.4% 2/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Psychiatric disorders Insomnia	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	3.4% 2/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/10 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/11 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/19 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	0.00% 0/21 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.	6.9% 4/58 • Double-blind Treatment Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) up to week 12 or the day before OLE day 1. Open-label Extension Period: From the start of the OLE (week 12) to end of study (week 54) for all-cause mortality (up to 42 weeks); 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 (a maximum of 40 weeks). Adverse events are reported for all participants who received at least one dose of study drug in each period. All-cause mortality is reported for all participants randomized in the double-blind treatment period and for all participants who entered the OLE period.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: medinfo@amgen.com

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