Trial Outcomes & Findings for A Study to Investigate the Efficacy and Safety of Baxdrostat in Participants With Uncontrolled Hypertension on Two or More Medications Including Participants With Resistant Hypertension (NCT NCT06034743)

Last Updated: 2026-07-30

Results Overview

To assess the effect of 2 mg baxdrostat versus placebo on seated systolic blood pressure at Week 12. All available measurements were included, and missing data were multiply imputed.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

796 participants

Primary outcome timeframe

At Week 12

Results posted on

2026-07-30

Participant Flow

The study was done from 22 November 2023 to 05 November 2025. Participants were screened and randomised from 269 study sites across 29 countries. A total of 794 participants were randomised and treated in the study.

Participants were screened for eligibility and entered a 2-week single-blind placebo run-in period. Both cohorts (Cohort 1 \[C1\] and Cohort 2 \[C2\]) completed a 12-week double-blind period (baxdrostat 2 mg, 1 mg, or placebo, 1:1:1) and a 12-week open-label period (baxdrostat 2 mg or standard of care). C1 participants on baxdrostat 2 mg at Week 24 also completed an 8-week randomised withdrawal period and a 20-week open-label extension; those on standard of care continued through Week 52.

Participant milestones

Participant milestones
Measure	Double-Blind Treatment Period Weeks 0-12 Baxdrostat 1mg Participants received a baxdrostat 1 mg tablet orally once daily. Participants from both Cohort 1 and Cohort 2 were randomized 1:1:1 to baxdrostat 1 mg, baxdrostat 2 mg, or placebo.	Double-Blind Treatment Period Weeks 0-12 Baxdrostat 2mg Participants received a baxdrostat 2 mg tablet orally once daily. Participants from both Cohort 1 and Cohort 2 were randomized 1:1:1 to baxdrostat 1 mg, baxdrostat 2 mg, or placebo.	Double-Blind Treatment Period Weeks 0-12 Placebo Participants received a placebo tablet orally once daily. Participants from both Cohort 1 and Cohort 2 were randomized 1:1:1 to baxdrostat 1 mg, baxdrostat 2 mg, or placebo.	Open-Label Period Weeks 13-24 Baxdrostat 2mg Participants received a baxdrostat 2 mg tablet orally once daily. After the initial double-blind period (Weeks 0-12), both Cohort 1 and Cohort 2 participants were randomised into this study period. Participants who received baxdrostat 2 mg in Weeks 0-12 continued baxdrostat 2 mg open-label. Participants who received baxdrostat 1 mg (4:1 allocation) or placebo (1:4 allocation) were randomised to either baxdrostat 2 mg open-label or standard-of-care (SOC).	Open-Label Period Weeks 13-52 Standard of Care Participants received standard of care antihypertensive medication. After the initial double-blind period (Weeks 0-12), Cohort 1 and Cohort 2 participants who received baxdrostat 1 mg (4:1 allocation) or placebo (1:4 allocation) were randomised to baxdrostat 2 mg open-label or SOC. In Cohort 1, SOC was received for 40 weeks (Weeks 13-52) followed by 2-week Safety Follow-up. In Cohort 2, SOC was received for 12 weeks (Weeks 13-24) followed by 2-week Safety Follow-up.	Randomised Withdrawal Period Weeks 25-32 Baxdrostat 2mg Participants received a baxdrostat 2 mg tablet orally once daily. After completing 12 weeks of open-label baxdrostat 2 mg (Weeks 13-24), Cohort 1 participants were randomised 2:1 at Week 24 to continue baxdrostat 2 mg or switch to placebo for an 8-week, double-blind randomized-withdrawal (Weeks 25-32).	Randomised Withdrawal Period Weeks 25-32 Placebo Participants received a placebo tablet orally once daily. After completing 12 weeks of open-label baxdrostat 2 mg (Weeks 13-24), Cohort 1 participants were randomised 2:1 at Week 24 to continue baxdrostat 2 mg or switch to placebo for an 8-week, double-blind randomized-withdrawal (Weeks 25-32).	Open-Label Period Weeks 33-52 Baxdrostat 2mg Participants received a baxdrostat 2 mg tablet orally once daily. After completing the 8-week randomised withdrawal (Weeks 25-32), regardless of the treatment assignment (baxdrostat 2 mg or placebo), Cohort 1 participants received baxdrostat 2 mg open-label for 20 weeks (Weeks 33-52) followed by 2-week Safety Follow-up.
Double-Blind Treatment Period Weeks 0-12 STARTED	264	266	264	0	0	0	0	0
Double-Blind Treatment Period Weeks 0-12 COMPLETED	245	237	246	0	0	0	0	0
Double-Blind Treatment Period Weeks 0-12 NOT COMPLETED	19	29	18	0	0	0	0	0
Open-Label Period Weeks 13-24 STARTED	0	0	0	483	0	0	0	0
Open-Label Period Weeks 13-24 COMPLETED	0	0	0	448	0	0	0	0
Open-Label Period Weeks 13-24 NOT COMPLETED	0	0	0	35	0	0	0	0
Open-Label Period Weeks 13-52 STARTED	0	0	0	0	245	0	0	0
Open-Label Period Weeks 13-52 COMPLETED	0	0	0	0	150	0	0	0
Open-Label Period Weeks 13-52 NOT COMPLETED	0	0	0	0	95	0	0	0
Randomised Withdrawal Period Weeks 25-32 STARTED	0	0	0	0	0	172	85	0
Randomised Withdrawal Period Weeks 25-32 COMPLETED	0	0	0	0	0	163	82	0
Randomised Withdrawal Period Weeks 25-32 NOT COMPLETED	0	0	0	0	0	9	3	0
Open-Label Period Weeks 33-52 STARTED	0	0	0	0	0	0	0	245
Open-Label Period Weeks 33-52 COMPLETED	0	0	0	0	0	0	0	90
Open-Label Period Weeks 33-52 NOT COMPLETED	0	0	0	0	0	0	0	155

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

One placebo participant did not have baseline seated SBP.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Double-Blind Treatment Period Weeks 0-12 Baxdrostat 1mg n=264 Participants Participants received a baxdrostat 1 mg tablet orally once daily.	Double-Blind Treatment Period Weeks 0-12 Baxdrostat 2mg n=266 Participants Participants received a baxdrostat 2 mg tablet orally once daily.	Double-Blind Treatment Period Weeks 0-12 Placebo n=264 Participants Participants received a placebo tablet orally once daily.	Total n=794 Participants Total of all reporting groups
Age, Continuous	59.8 Years STANDARD_DEVIATION 11.8 • n=264 Participants	61.8 Years STANDARD_DEVIATION 11.7 • n=266 Participants	61.9 Years STANDARD_DEVIATION 11.6 • n=264 Participants	61.1 Years STANDARD_DEVIATION 11.7 • n=794 Participants
Sex: Female, Male Female	95 Participants n=264 Participants	103 Participants n=266 Participants	102 Participants n=264 Participants	300 Participants n=794 Participants
Sex: Female, Male Male	169 Participants n=264 Participants	163 Participants n=266 Participants	162 Participants n=264 Participants	494 Participants n=794 Participants
Race/Ethnicity, Customized Race : American Indian or Alaska Native	0 Participants n=264 Participants	0 Participants n=266 Participants	0 Participants n=264 Participants	0 Participants n=794 Participants
Race/Ethnicity, Customized Race : Asian	65 Participants n=264 Participants	72 Participants n=266 Participants	72 Participants n=264 Participants	209 Participants n=794 Participants
Race/Ethnicity, Customized Race : Black or African American	23 Participants n=264 Participants	21 Participants n=266 Participants	15 Participants n=264 Participants	59 Participants n=794 Participants
Race/Ethnicity, Customized Race : Native Hawaiian or Other Pacific Islander	1 Participants n=264 Participants	0 Participants n=266 Participants	1 Participants n=264 Participants	2 Participants n=794 Participants
Race/Ethnicity, Customized Race : White	165 Participants n=264 Participants	168 Participants n=266 Participants	167 Participants n=264 Participants	500 Participants n=794 Participants
Race/Ethnicity, Customized Race : Multiple	1 Participants n=264 Participants	1 Participants n=266 Participants	0 Participants n=264 Participants	2 Participants n=794 Participants
Race/Ethnicity, Customized Race : Other	8 Participants n=264 Participants	1 Participants n=266 Participants	7 Participants n=264 Participants	16 Participants n=794 Participants
Race/Ethnicity, Customized Race : Missing	1 Participants n=264 Participants	3 Participants n=266 Participants	2 Participants n=264 Participants	6 Participants n=794 Participants
Race/Ethnicity, Customized Ethnicity : Hispanic or Latino	27 Participants n=264 Participants	39 Participants n=266 Participants	38 Participants n=264 Participants	104 Participants n=794 Participants
Race/Ethnicity, Customized Ethnicity : Not Hispanic or Latino	231 Participants n=264 Participants	216 Participants n=266 Participants	216 Participants n=264 Participants	663 Participants n=794 Participants
Race/Ethnicity, Customized Ethnicity : Missing	6 Participants n=264 Participants	11 Participants n=266 Participants	10 Participants n=264 Participants	27 Participants n=794 Participants
Seated Systolic Blood Pressure	149.7 mmHg STANDARD_DEVIATION 10.1 • n=264 Participants • One placebo participant did not have baseline seated SBP.	149.1 mmHg STANDARD_DEVIATION 9.1 • n=266 Participants • One placebo participant did not have baseline seated SBP.	149.0 mmHg STANDARD_DEVIATION 8.7 • n=263 Participants • One placebo participant did not have baseline seated SBP.	149.3 mmHg STANDARD_DEVIATION 9.3 • n=793 Participants • One placebo participant did not have baseline seated SBP.

PRIMARY outcome

Timeframe: At Week 12

Population: The Full Analysis Set included all randomised participants who received at least one administration of investigational medicinal product. One placebo participant did not have baseline seated SBP and therefore was excluded from primary endpoint analysis.

To assess the effect of 2 mg baxdrostat versus placebo on seated systolic blood pressure at Week 12. All available measurements were included, and missing data were multiply imputed.

Outcome measures

Outcome measures
Measure	Randomised Withdrawal Period Weeks 25-32 Baxdrostat 2mg n=266 Participants Participants received a baxdrostat 2 mg tablet orally once daily.	Randomised Withdrawal Period Weeks 25-32 Placebo n=263 Participants Participants received a placebo tablet orally once daily.
Change From Baseline in Seated Systolic Blood Pressure for 2 mg Baxdrostat	-15.7 mmHg Standard Error 1.0	-5.8 mmHg Standard Error 1.0

PRIMARY outcome

Timeframe: At Week 12

To assess the effect of 1 mg baxdrostat versus placebo on seated systolic blood pressure at Week 12. All available measurements were included, and missing data were multiply imputed.

Outcome measures

Outcome measures
Measure	Randomised Withdrawal Period Weeks 25-32 Baxdrostat 2mg n=264 Participants Participants received a baxdrostat 2 mg tablet orally once daily.	Randomised Withdrawal Period Weeks 25-32 Placebo n=263 Participants Participants received a placebo tablet orally once daily.
Change From Baseline in Seated Systolic Blood Pressure for 1 mg Baxdrostat	-14.5 mmHg Standard Error 1.0	-5.8 mmHg Standard Error 1.0

SECONDARY outcome

Timeframe: At Week 32

Population: The RWD Set included all participants who were randomised into the RWD period and have received at least one dose of investigational medicinal product in the RWD period.

To assess the effect of 2 mg baxdrostat vs placebo on seated systolic blood pressure (SBP) at 8 weeks after randomised withdrawal (RWD). All available measurements were included, and missing data were multiply imputed.

Outcome measures

Outcome measures
Measure	Randomised Withdrawal Period Weeks 25-32 Baxdrostat 2mg n=172 Participants Participants received a baxdrostat 2 mg tablet orally once daily.	Randomised Withdrawal Period Weeks 25-32 Placebo n=85 Participants Participants received a placebo tablet orally once daily.
Change From Randomised Withdrawal Baseline (Week 24) in Seated Systolic Blood Pressure (SBP) for 2 mg Baxdrostat	-3.7 mmHg Standard Error 0.9	1.4 mmHg Standard Error 1.3

SECONDARY outcome

Timeframe: At Week 12

Population: Included only participants with resistant hypertension at baseline in the Full Analysis Set which included all randomised participants who received at least one administration of investigational medicinal product.

To assess the effect of 2 mg baxdrostat vs placebo on seated SBP at Week 12 in the resistant hypertension (rHTN) subpopulation. All available measurements were included, and missing data were multiply imputed.

Outcome measures

Outcome measures
Measure	Randomised Withdrawal Period Weeks 25-32 Baxdrostat 2mg n=199 Participants Participants received a baxdrostat 2 mg tablet orally once daily.	Randomised Withdrawal Period Weeks 25-32 Placebo n=192 Participants Participants received a placebo tablet orally once daily.
Change From Baseline in Seated SBP for 2 mg Baxdrostat in the Resistant Hypertension Subpopulation	-15.2 mmHg Standard Error 1.2	-5.4 mmHg Standard Error 1.3

SECONDARY outcome

Timeframe: At Week 12

Population: The Full Analysis Set which included all randomised participants who received at least one administration of investigational medicinal product. One placebo participant did not have baseline seated SBP and therefore was excluded from secondary endpoint analysis.

To assess the effect of 2 mg baxdrostat vs placebo on seated diastolic blood pressure (DBP) at Week 12. All available measurements were included, and missing data were multiply imputed.

Outcome measures

Outcome measures
Measure	Randomised Withdrawal Period Weeks 25-32 Baxdrostat 2mg n=266 Participants Participants received a baxdrostat 2 mg tablet orally once daily.	Randomised Withdrawal Period Weeks 25-32 Placebo n=263 Participants Participants received a placebo tablet orally once daily.
Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 2 mg Baxdrostat	-6.9 mmHg Standard Error 0.6	-3.0 mmHg Standard Error 0.7

SECONDARY outcome

Timeframe: At Week 12

Population: Included participants with baseline seated SBP of 130 mmHg or higher in the Full Analysis Set which included all randomised participants who received at least one administration of investigational medicinal product.

To assess the effect of 2 mg baxdrostat vs placebo on achieving seated SBP \< 130 mmHg at Week 12. All available measurements were included, and missing data were multiply imputed.

Outcome measures

Outcome measures
Measure	Randomised Withdrawal Period Weeks 25-32 Baxdrostat 2mg n=265 Participants Participants received a baxdrostat 2 mg tablet orally once daily.	Randomised Withdrawal Period Weeks 25-32 Placebo n=262 Participants Participants received a placebo tablet orally once daily.
Number of Participants Who Achieved Seated SBP < 130 mmHg for 2 mg Baxdrostat	106 Participants	49 Participants

SECONDARY outcome

Timeframe: At Week 12

To assess the effect of 1 mg baxdrostat vs placebo on seated SBP at Week 12 in the resistant hypertension (rHTN) subpopulation. All available measurements were included, and missing data were multiply imputed.

Outcome measures

Outcome measures
Measure	Randomised Withdrawal Period Weeks 25-32 Baxdrostat 2mg n=187 Participants Participants received a baxdrostat 2 mg tablet orally once daily.	Randomised Withdrawal Period Weeks 25-32 Placebo n=192 Participants Participants received a placebo tablet orally once daily.
Change From Baseline in Seated SBP for 1 mg Baxdrostat in the Resistant Hypertension Subpopulation	-14.5 mmHg Standard Error 1.2	-5.4 mmHg Standard Error 1.3

SECONDARY outcome

Timeframe: At Week 12

To assess the effect of 1 mg baxdrostat vs placebo on seated diastolic blood pressure (DBP) at Week 12. All available measurements were included, and missing data were multiply imputed.

Outcome measures

Outcome measures
Measure	Randomised Withdrawal Period Weeks 25-32 Baxdrostat 2mg n=264 Participants Participants received a baxdrostat 2 mg tablet orally once daily.	Randomised Withdrawal Period Weeks 25-32 Placebo n=263 Participants Participants received a placebo tablet orally once daily.
Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 1 mg Baxdrostat	-6.3 mmHg Standard Error 0.7	-3.0 mmHg Standard Error 0.7

SECONDARY outcome

Timeframe: At Week 12

To assess the effect of 1 mg baxdrostat vs placebo on achieving seated SBP \< 130 mmHg at Week 12. All available measurements were included, and missing data were multiply imputed.

Outcome measures

Outcome measures
Measure	Randomised Withdrawal Period Weeks 25-32 Baxdrostat 2mg n=264 Participants Participants received a baxdrostat 2 mg tablet orally once daily.	Randomised Withdrawal Period Weeks 25-32 Placebo n=262 Participants Participants received a placebo tablet orally once daily.
Number of Participants Who Achieved Seated SBP < 130 mmHg for 1 mg Baxdrostat	104 Participants	49 Participants

Adverse Events

Double-Blind Treatment Period Weeks 0-12 Baxdrostat 1mg

Serious events: 5 serious events

Other events: 38 other events

Deaths: 0 deaths

Double-Blind Treatment Period Weeks 0-12 Baxdrostat 2mg

Serious events: 9 serious events

Other events: 55 other events

Deaths: 0 deaths

Double-Blind Treatment Period Weeks 0-12 Placebo

Serious events: 7 serious events

Other events: 29 other events

Deaths: 1 deaths

Randomised Withdrawal Period Weeks 25-32 Baxdrostat 2mg

Serious events: 4 serious events

Other events: 28 other events

Deaths: 0 deaths

Randomised Withdrawal Period Weeks 25-32 Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Weeks 0-24 Analysis Period Baxdrostat

Serious events: 32 serious events

Other events: 120 other events

Deaths: 0 deaths

Weeks 0-24 Analysis Period Placebo/Standard of Care

Serious events: 13 serious events

Other events: 32 other events

Deaths: 1 deaths

Weeks 0-52 Analysis Period Baxdrostat

Serious events: 9 serious events

Other events: 32 other events

Deaths: 0 deaths

Weeks 0-52 Analysis Period Placebo/Standard of Care

Serious events: 5 serious events

Other events: 9 other events

Deaths: 0 deaths

Weeks 13-52 Analysis Period Baxdrostat 2mg

Serious events: 3 serious events

Other events: 24 other events

Deaths: 0 deaths

Weeks 13-52 Analysis Period Standard of Care

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Double-Blind Treatment Period Weeks 0-12 Baxdrostat 1mg n=264 participants at risk Participants received a baxdrostat 1mg tablet orally once daily during double-blind treament period (0-12 weeks).	Double-Blind Treatment Period Weeks 0-12 Baxdrostat 2mg n=266 participants at risk Participants received a baxdrostat 2 mg tablet orally once daily.	Double-Blind Treatment Period Weeks 0-12 Placebo n=264 participants at risk Participants received a placebo tablet orally once daily during double-blind treament period (0-12 weeks).	Randomised Withdrawal Period Weeks 25-32 Baxdrostat 2mg n=172 participants at risk Participants received a baxdrostat 2mg tablet orally once daily during randomised withdrawal period (25-32 weeks).	Randomised Withdrawal Period Weeks 25-32 Placebo n=85 participants at risk Participants received a placebo tablet orally once daily during randomised withdrawal period (25-32 weeks).	Weeks 0-24 Analysis Period Baxdrostat n=466 participants at risk Participants received either a baxdrostat 1mg or 2mg tablet orally once daily during the double-blind treatment period (0-12 weeks) and a baxdrostat 2mg tablet orally once daily during the open-label period (13-24 weeks).	Weeks 0-24 Analysis Period Placebo/Standard of Care n=208 participants at risk Participants received a placebo tablet orally once daily during the double-blind treatment period (0-12 weeks) and standard of care during the open-label period (13-24 weeks).	Weeks 0-52 Analysis Period Baxdrostat n=73 participants at risk Participants received orally once daily either a baxdrostat 1mg or 2mg tablet during the double-blind treatment period (0-12 weeks), a baxdrostat 2mg tablet during the open-label period (13-24 weeks), a baxdrostat 2mg tablet during the randomised withdrawal period (25-32 weeks), and a baxdrostat 2mg tablet during the open-label period (33-52 weeks).	Weeks 0-52 Analysis Period Placebo/Standard of Care n=47 participants at risk Participants received a placebo tablet orally once daily during the double-blind treatment period (0-12 weeks) and standard of care during the open-label period (13-52 weeks).	Weeks 13-52 Analysis Period Baxdrostat 2mg n=62 participants at risk Participants received orally once daily either a placebo tablet during the double-blind treatment period (0-12 weeks) and a baxdrostat 2mg tablet during the open-label period (13-24 weeks), or a placebo tablet during the randomised withdrawal period (25-32 weeks).	Weeks 13-52 Analysis Period Standard of Care n=29 participants at risk Participants received a baxdrostat 1mg tablet orally once daily during the double-blind treatment period (0-12 weeks) and standard of care during the open-label period (13-52 weeks).
Cardiac disorders Acute myocardial infarction	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.48% 1/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	2.1% 1/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Cardiac disorders Angina pectoris	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.43% 2/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	2.7% 2/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Cardiac disorders Atrial fibrillation	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.48% 1/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Cardiac disorders Cardiac failure	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.96% 2/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	4.3% 2/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Cardiac disorders Myocardial infarction	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.48% 1/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Cardiac disorders Sinus node dysfunction	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.48% 1/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Gastrointestinal disorders Diarrhoea	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Gastrointestinal disorders Dyspepsia	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Gastrointestinal disorders Gastritis	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.48% 1/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	2.1% 1/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Gastrointestinal disorders Haemorrhoids	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.96% 2/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	2.1% 1/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Gastrointestinal disorders Inguinal hernia	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.48% 1/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.6% 1/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Gastrointestinal disorders Obstructive pancreatitis	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.48% 1/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.43% 2/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.4% 1/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
General disorders Non-cardiac chest pain	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.43% 2/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Infections and infestations Escherichia urinary tract infection	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.6% 1/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Infections and infestations Enteritis infectious	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.58% 1/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.6% 1/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Infections and infestations Herpes zoster disseminated	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.4% 1/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Infections and infestations Lower respiratory tract infection	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Infections and infestations Pneumonia	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.48% 1/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Infections and infestations Pneumonia staphylococcal	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Infections and infestations Postoperative abscess	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.4% 1/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Infections and infestations Septic shock	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.76% 2/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.96% 2/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Infections and infestations Typhoid fever	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Infections and infestations Urinary tract infection	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.4% 1/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.48% 1/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	2.1% 1/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.4% 1/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Metabolism and nutrition disorders Hyperkalaemia	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.43% 2/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Metabolism and nutrition disorders Hypervolaemia	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.76% 2/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.96% 2/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	2.1% 1/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Metabolism and nutrition disorders Hyponatraemia	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.43% 2/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	2.1% 1/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.58% 1/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Clear cell renal cell carcinoma	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.4% 1/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Large intestine benign neoplasm	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.58% 1/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.4% 1/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.4% 1/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.4% 1/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Nervous system disorders Altered state of consciousness	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Nervous system disorders Cerebral artery embolism	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	3.4% 1/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Nervous system disorders Ischaemic stroke	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.48% 1/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Nervous system disorders Sciatica	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Nervous system disorders Transient ischaemic attack	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.43% 2/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.4% 1/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Renal and urinary disorders Acute kidney injury	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.4% 1/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Renal and urinary disorders Chronic kidney disease	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	2.1% 1/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Renal and urinary disorders Nephrolithiasis	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.48% 1/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.48% 1/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.48% 1/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.58% 1/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.4% 1/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.48% 1/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Vascular disorders Aortic aneurysm	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	2.1% 1/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Vascular disorders Hypertension	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.75% 2/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.43% 2/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.4% 1/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Vascular disorders Hypertensive urgency	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Vascular disorders Hypotension	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.58% 1/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.4% 1/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.

Other adverse events

Other adverse events
Measure	Double-Blind Treatment Period Weeks 0-12 Baxdrostat 1mg n=264 participants at risk Participants received a baxdrostat 1mg tablet orally once daily during double-blind treament period (0-12 weeks).	Double-Blind Treatment Period Weeks 0-12 Baxdrostat 2mg n=266 participants at risk Participants received a baxdrostat 2 mg tablet orally once daily.	Double-Blind Treatment Period Weeks 0-12 Placebo n=264 participants at risk Participants received a placebo tablet orally once daily during double-blind treament period (0-12 weeks).	Randomised Withdrawal Period Weeks 25-32 Baxdrostat 2mg n=172 participants at risk Participants received a baxdrostat 2mg tablet orally once daily during randomised withdrawal period (25-32 weeks).	Randomised Withdrawal Period Weeks 25-32 Placebo n=85 participants at risk Participants received a placebo tablet orally once daily during randomised withdrawal period (25-32 weeks).	Weeks 0-24 Analysis Period Baxdrostat n=466 participants at risk Participants received either a baxdrostat 1mg or 2mg tablet orally once daily during the double-blind treatment period (0-12 weeks) and a baxdrostat 2mg tablet orally once daily during the open-label period (13-24 weeks).	Weeks 0-24 Analysis Period Placebo/Standard of Care n=208 participants at risk Participants received a placebo tablet orally once daily during the double-blind treatment period (0-12 weeks) and standard of care during the open-label period (13-24 weeks).	Weeks 0-52 Analysis Period Baxdrostat n=73 participants at risk Participants received orally once daily either a baxdrostat 1mg or 2mg tablet during the double-blind treatment period (0-12 weeks), a baxdrostat 2mg tablet during the open-label period (13-24 weeks), a baxdrostat 2mg tablet during the randomised withdrawal period (25-32 weeks), and a baxdrostat 2mg tablet during the open-label period (33-52 weeks).	Weeks 0-52 Analysis Period Placebo/Standard of Care n=47 participants at risk Participants received a placebo tablet orally once daily during the double-blind treatment period (0-12 weeks) and standard of care during the open-label period (13-52 weeks).	Weeks 13-52 Analysis Period Baxdrostat 2mg n=62 participants at risk Participants received orally once daily either a placebo tablet during the double-blind treatment period (0-12 weeks) and a baxdrostat 2mg tablet during the open-label period (13-24 weeks), or a placebo tablet during the randomised withdrawal period (25-32 weeks).	Weeks 13-52 Analysis Period Standard of Care n=29 participants at risk Participants received a baxdrostat 1mg tablet orally once daily during the double-blind treatment period (0-12 weeks) and standard of care during the open-label period (13-52 weeks).
Infections and infestations Nasopharyngitis	3.0% 8/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	3.0% 8/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	2.3% 6/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.7% 3/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.2% 1/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	4.7% 22/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	3.4% 7/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	4.1% 3/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	6.4% 3/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	6.5% 4/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Infections and infestations Upper respiratory tract infection	2.7% 7/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	3.8% 10/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.58% 1/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.2% 1/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.5% 7/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	5.3% 11/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	5.5% 4/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	8.5% 4/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	3.2% 2/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	10.3% 3/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Metabolism and nutrition disorders Hyperkalaemia	6.1% 16/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	11.7% 31/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	2.7% 7/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	9.9% 17/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	4.7% 4/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	14.6% 68/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	2.9% 6/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	26.0% 19/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	2.1% 1/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	16.1% 10/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	6.9% 2/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Metabolism and nutrition disorders Hyponatraemia	1.1% 3/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	3.8% 10/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.76% 2/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	3.5% 6/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	2.4% 2/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	4.3% 20/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.48% 1/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	4.1% 3/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	2.1% 1/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	11.3% 7/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	3.4% 1/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Musculoskeletal and connective tissue disorders Arthralgia	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	2.3% 6/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.76% 2/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.58% 1/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.7% 8/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.96% 2/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	6.8% 5/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Musculoskeletal and connective tissue disorders Muscle spasms	2.3% 6/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	3.8% 10/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.38% 1/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.58% 1/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.2% 1/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	4.1% 19/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.4% 3/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	4.1% 3/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	6.5% 4/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.
Skin and subcutaneous tissue disorders Rash	0.00% 0/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/266 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.76% 2/264 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.58% 1/172 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	1.2% 1/85 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.21% 1/466 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.96% 2/208 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/73 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/47 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	6.5% 4/62 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.	0.00% 0/29 • From first dose of study drug to the end of study at Week 54. Note that the study was analyzed in five analysis periods: Double-Blind Treatment Weeks 0-12 (both cohorts), RWD Weeks 25-32 (C1 only), Weeks 0-24 (both cohorts; including the 2-week safety follow-up (SFU) period till Week 26 for C2), Weeks 0-52 (C1 only; including the 2-week SFU period till Week 54 for C1) and Weeks 13-52 (both cohorts; including the 2-week SFU period till Week 26 for C2 and Week 54 for C1). Adverse events are reported by pre-specified analysis periods, not individual study periods. The 12-week double-blind and randomised withdrawal periods report AEs by treatment arm for those periods. The Weeks 0-24, 0-52, and 13-52 analysis periods report cumulative AEs for defined participant subsets across sequential treatment phases, as pre-specified in the Statistical Analysis Plan (Section 4.6). An adverse event may appear in multiple analysis periods due to overlapping period definitions.

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-887-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No unpublished information may be disclosed without prior written approval from AstraZeneca.
Publication restrictions are in place

Restriction type: OTHER