Trial Outcomes & Findings for A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial (NCT NCT04847557)

NCT ID: NCT04847557

Last Updated: 2025-08-20

Results Overview

The KCCQ is a 23-item, participant self-administered questionnaire that assesses impacts of heart failure "over the past 2 weeks" on the following 7 domains: * Physical Limitation (6) * Symptom Stability (1) * Symptom Frequency (4) * Symptom Burden (3) * Self-Efficacy (2) * Quality of Life (3) * Social Limitation (4) Each of the 23 individual items are answered on Likert scales of varying lengths (5, 6, or 7-point scales). KCCQ-CSS includes the symptom and physical limitation domains of the KCCQ. Scores are obtained by averaging the associated individual items and transforming the score to a 0 to 100 range. Higher scores indicate better health status. Least Square (LS) mean was determined using ANCOVA model with Baseline + HF Decompensation Within 12 Months of Screening + T2DM Status + Baseline BMI group (\<35, \>=35 kg/m2) + Treatment (Type III sum of squares) as variables .

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 731 participants
• Primary outcome timeframe: Baseline, Week 52
• Results posted on: 2025-08-20

Participant Flow

Participant milestones

Measure	Tirzepatide - MTD Participants received a starting dose of 2.5 milligrams (mg) tirzepatide administered subcutaneously (SC) once weekly (QW) and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or maximum tolerated dose (MTD) tolerated by the participant (5 mg QW or 10 mg QW).	Placebo Participants received placebo administered SC QW.
Overall Study STARTED	364	367
Overall Study Received At Least One Dose of Study Drug	364	367
Overall Study COMPLETED	332	331
Overall Study NOT COMPLETED	32	36

Reasons for withdrawal

Measure	Tirzepatide - MTD Participants received a starting dose of 2.5 milligrams (mg) tirzepatide administered subcutaneously (SC) once weekly (QW) and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or maximum tolerated dose (MTD) tolerated by the participant (5 mg QW or 10 mg QW).	Placebo Participants received placebo administered SC QW.
Overall Study Adverse Event	1	0
Overall Study Death	19	15
Overall Study Lost to Follow-up	3	6
Overall Study Physician Decision	1	0
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	8	14

Baseline Characteristics

A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial

Baseline characteristics by cohort

Measure	Tirzepatide - MTD n=364 Participants Participants received a starting dose of 2.5 mg tirzepatide administered SC QW and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or MTD tolerated by the participant (5 mg QW or 10 mg QW).	Placebo n=367 Participants Participants received placebo administered SC QW.	Total n=731 Participants Total of all reporting groups
Age, Continuous	65.50 years STANDARD_DEVIATION 10.53 • n=5 Participants	65.00 years STANDARD_DEVIATION 10.87 • n=7 Participants	65.20 years STANDARD_DEVIATION 10.70 • n=5 Participants
Sex: Female, Male Female	200 Participants n=5 Participants	193 Participants n=7 Participants	393 Participants n=5 Participants
Sex: Female, Male Male	164 Participants n=5 Participants	174 Participants n=7 Participants	338 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	195 Participants n=5 Participants	205 Participants n=7 Participants	400 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	164 Participants n=5 Participants	159 Participants n=7 Participants	323 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	24 Participants n=5 Participants	23 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) Asian	58 Participants n=5 Participants	73 Participants n=7 Participants	131 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	22 Participants n=5 Participants	14 Participants n=7 Participants	36 Participants n=5 Participants
Race (NIH/OMB) White	256 Participants n=5 Participants	256 Participants n=7 Participants	512 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Argentina	101 Participants n=5 Participants	103 Participants n=7 Participants	204 Participants n=5 Participants
Region of Enrollment Brazil	51 Participants n=5 Participants	54 Participants n=7 Participants	105 Participants n=5 Participants
Region of Enrollment China	25 Participants n=5 Participants	30 Participants n=7 Participants	55 Participants n=5 Participants
Region of Enrollment India	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment Israel	17 Participants n=5 Participants	21 Participants n=7 Participants	38 Participants n=5 Participants
Region of Enrollment Mexico	41 Participants n=5 Participants	40 Participants n=7 Participants	81 Participants n=5 Participants
Region of Enrollment Russia	13 Participants n=5 Participants	8 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment Taiwan	24 Participants n=5 Participants	32 Participants n=7 Participants	56 Participants n=5 Participants
Region of Enrollment United States	83 Participants n=5 Participants	68 Participants n=7 Participants	151 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 52

Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.

The KCCQ is a 23-item, participant self-administered questionnaire that assesses impacts of heart failure "over the past 2 weeks" on the following 7 domains:

• Physical Limitation (6)
• Symptom Stability (1)
• Symptom Frequency (4)
• Symptom Burden (3)
• Self-Efficacy (2)
• Quality of Life (3)
• Social Limitation (4)

Each of the 23 individual items are answered on Likert scales of varying lengths (5, 6, or 7-point scales).

KCCQ-CSS includes the symptom and physical limitation domains of the KCCQ. Scores are obtained by averaging the associated individual items and transforming the score to a 0 to 100 range. Higher scores indicate better health status.

Least Square (LS) mean was determined using ANCOVA model with Baseline + HF Decompensation Within 12 Months of Screening + T2DM Status + Baseline BMI group (<35, >=35 kg/m2) + Treatment (Type III sum of squares) as variables .

Outcome measures

Measure	Tirzepatide - MTD n=301 Participants Participants received a starting dose of 2.5 mg tirzepatide administered SC QW and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or MTD tolerated by the participant (5 mg QW or 10 mg QW).	Placebo n=313 Participants Participants received placebo administered SC QW.
Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS)	19.51 Score on a scale Standard Error 1.24	12.68 Score on a scale Standard Error 1.25

PRIMARY outcome

Timeframe: Baseline Up To 160 weeks

Population: All participants who received at least one dose of study drug.

Clinical Endpoint Committe confirmed Occurrences of CV outcomes were reported here. HF outcomes consisted of cardiovascular death and HF events.

The HF events were defined as worsening clinical symptoms or signs related to HF, which are meaningful to the participant and require intensification of treatment characterized by 1 or more of the following:

• hospitalization for heart failure regardless of duration or treatment received
• use of intravenous drug, usually an intravenous diuretic, but may include intravenous vasodilators or positive inotropic drugs, or
• augmentation or increase in oral diuretic therapy.

Outcome measures

Measure	Tirzepatide - MTD n=364 Participants Participants received a starting dose of 2.5 mg tirzepatide administered SC QW and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or MTD tolerated by the participant (5 mg QW or 10 mg QW).	Placebo n=367 Participants Participants received placebo administered SC QW.
First Occurrence of the Composite Endpoint of Heart Failure (HF) Outcomes	36 Number of events	56 Number of events

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All participants who received at least one dose of study drug and had evaluable data for this outcome,

Participants performed an exercise capacity assessment using the 6-Minute Walk Test (6MWT) and the distance covered (6MWD) was assessed in meters. The 6MWT was performed indoors on a straight, flat, hard surface that is at least 30 meters in length. The greater distance walked meant better physical capacity.

LS Mean was determined using ANCOVA model with Baseline + HF Decompensation Within 12 Months of Screening + T2DM Status + Baseline BMI group (<35, >=35 kg/m2) + Treatment (Type III sum of squares) as variables.

Outcome measures

Measure	Tirzepatide - MTD n=326 Participants Participants received a starting dose of 2.5 mg tirzepatide administered SC QW and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or MTD tolerated by the participant (5 mg QW or 10 mg QW).	Placebo n=314 Participants Participants received placebo administered SC QW.
Change From Baseline in Exercise Capacity as Measured by 6-Minute Walk Distance (6MWD)	26.04 meters Standard Error 3.81	10.10 meters Standard Error 3.94

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.

Percent change in bodyweight was reported. LS mean was determined using ANCOVA model with Baseline + HF Decompensation Within 12 Months of Screening + T2DM Status + Baseline BMI group (<35, >=35 kg/m2) + Treatment (Type III sum of squares) as variables.

Outcome measures

Measure	Tirzepatide - MTD n=331 Participants Participants received a starting dose of 2.5 mg tirzepatide administered SC QW and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or MTD tolerated by the participant (5 mg QW or 10 mg QW).	Placebo n=333 Participants Participants received placebo administered SC QW.
Percent Change From Baseline in Body Weight	-13.85 Percent change Standard Error 0.43	-2.24 Percent change Standard Error 0.46

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.

Percent change from baseline in hsCRP was reported. LS Mean was determined using ANCOVA model with log (actual measurement/baseline) = log (baseline) + HF decompensation within 12 months of screening + T2DM status + baseline BMI group (<35, >=35 kg/m2) + Treatment (Type III sum of squares) as variables.

Outcome measures

Measure	Tirzepatide - MTD n=305 Participants Participants received a starting dose of 2.5 mg tirzepatide administered SC QW and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or MTD tolerated by the participant (5 mg QW or 10 mg QW).	Placebo n=298 Participants Participants received placebo administered SC QW.
Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)	-38.76 Percent change Standard Error 4.47	-5.88 Percent change Standard Error 5.25

SECONDARY outcome

Timeframe: Baseline Up To 160 Weeks

Population: All participants who received at least one dose of study drug.

Hierarchical Composite Endpoint included time to all-cause death, number of HF events, time to first HF events, KCCQ-CSS, 6MWD.

The winner was determined in each pair-wise comparison in the following order:

• A delayed first occurrence of all-cause death
• If the pair cannot be differentiated based on death, winner has fewer HF events
• If the pair cannot be differentiated by number of HF events, winner has delayed time to occurrence of first HF event
• If the pair still cannot be differentiated, winner has a more favorable category for change from baseline in 6MWD
• If the pair still cannot be differentiated, winner has a more favorable category for change from baseline in KCCQ-CSS
• Otherwise the pair will be recorded as tied.

Reported unit is the total percent of "wins" for each treatment group from performing such a hierarchical comparison across stratification factors in the study.

Outcome measures

Measure	Tirzepatide - MTD n=364 Participants Participants received a starting dose of 2.5 mg tirzepatide administered SC QW and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or MTD tolerated by the participant (5 mg QW or 10 mg QW).	Placebo n=367 Participants Participants received placebo administered SC QW.
Win Percentage of the Hierarchical Composite Endpoint	57.90 Win percentage	35.43 Win percentage

SECONDARY outcome

Timeframe: Week 52

Population: All participant who received at least one dose of study drug and had evaluable data for this outcome.

Percentage of participants with NYHA class change at Week 52 was reported.

Outcome measures

Measure	Tirzepatide - MTD n=328 Participants Participants received a starting dose of 2.5 mg tirzepatide administered SC QW and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or MTD tolerated by the participant (5 mg QW or 10 mg QW).	Placebo n=327 Participants Participants received placebo administered SC QW.
Percentage of Participants With New York Heart Association (NYHA) Class Change	33.27 Percentage of participants	20.39 Percentage of participants

SECONDARY outcome

Timeframe: Baseline Up To 160 Weeks

Population: All participants who received at least one dose of study drug.

All-cause mortality is death due to any cause. Number of participants with time to all-cause mortality are presented.

Outcome measures

Measure	Tirzepatide - MTD n=364 Participants Participants received a starting dose of 2.5 mg tirzepatide administered SC QW and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or MTD tolerated by the participant (5 mg QW or 10 mg QW).	Placebo n=367 Participants Participants received placebo administered SC QW.
Number of Participants With Time to All-Cause Death	19 Participants	15 Participants

SECONDARY outcome

Timeframe: Baseline Up To 160 Weeks

Population: All participants who received at least one dose of study drug.

Number of participants with time to first occurrence of HF events are reported.

Outcome measures

Measure	Tirzepatide - MTD n=364 Participants Participants received a starting dose of 2.5 mg tirzepatide administered SC QW and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or MTD tolerated by the participant (5 mg QW or 10 mg QW).	Placebo n=367 Participants Participants received placebo administered SC QW.
Number of Participants With Time to First Occurrence of HF Events	29 Participants	52 Participants

SECONDARY outcome

Timeframe: Baseline Up To 160 Weeks.

Population: All participants who received at least one dose of study drug.

Number of HF events and all-cause death are reported.

Outcome measures

Measure	Tirzepatide - MTD n=364 Participants Participants received a starting dose of 2.5 mg tirzepatide administered SC QW and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or MTD tolerated by the participant (5 mg QW or 10 mg QW).	Placebo n=367 Participants Participants received placebo administered SC QW.
Number of HF Events and All-Cause Death	61 Events	82 Events

SECONDARY outcome

Timeframe: Baseline Up To 160 Weeks.

Population: All participants who received at least one dose of study drug.

Number of recurrent HF events were reported.

Outcome measures

Measure	Tirzepatide - MTD n=364 Participants Participants received a starting dose of 2.5 mg tirzepatide administered SC QW and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or MTD tolerated by the participant (5 mg QW or 10 mg QW).	Placebo n=367 Participants Participants received placebo administered SC QW.
Number of Recurrent HF Events	44 Events	68 Events

Adverse Events

Tirzepatide - MTD

Serious events: 96 serious events

Other events: 221 other events

Deaths: 19 deaths

Placebo

Serious events: 94 serious events

Other events: 137 other events

Deaths: 15 deaths

Serious adverse events

Measure	Tirzepatide - MTD n=364 participants at risk Participants received a starting dose of 2.5 mg tirzepatide administered SC QW and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or MTD tolerated by the participant (5 mg QW or 10 mg QW).	Placebo n=367 participants at risk Participants received placebo administered SC QW.
Hepatobiliary disorders Cholecystitis acute	1.6% 6/364 • Number of events 6 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	1.1% 4/367 • Number of events 4 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Hepatobiliary disorders Cholecystitis chronic	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Peptic ulcer haemorrhage	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Pneumoperitoneum	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Umbilical hernia	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.27% 1/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.54% 2/367 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Varices oesophageal	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Vomiting	0.27% 1/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
General disorders Chest pain	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
General disorders Pacemaker syndrome	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
General disorders Pyrexia	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
General disorders Sudden cardiac death	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
General disorders Sudden death	0.55% 2/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
General disorders Swelling face	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
General disorders Systemic inflammatory response syndrome	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Hepatobiliary disorders Cholecystitis	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Hepatobiliary disorders Acute hepatic failure	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Blood and lymphatic system disorders Anaemia	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	1.4% 5/367 • Number of events 7 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Acute coronary syndrome	0.55% 2/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Acute myocardial infarction	1.6% 6/364 • Number of events 6 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.54% 2/367 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Angina pectoris	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Angina unstable	0.82% 3/364 • Number of events 3 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	1.4% 5/367 • Number of events 5 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Atrial fibrillation	1.9% 7/364 • Number of events 9 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.82% 3/367 • Number of events 3 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Atrial flutter	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Atrioventricular block complete	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Bradycardia	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Cardiac arrest	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Cardiac failure	3.3% 12/364 • Number of events 17 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	4.9% 18/367 • Number of events 27 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Cardiac failure acute	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Cardiac failure chronic	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Cardiac failure congestive	0.82% 3/364 • Number of events 4 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	3.3% 12/367 • Number of events 18 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Cardiac valve disease	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Cardio-respiratory arrest	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.54% 2/367 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Cardiogenic shock	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Coronary artery disease	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.54% 2/367 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Heart failure with preserved ejection fraction	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Myocarditis	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Paroxysmal atrioventricular block	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Sinus node dysfunction	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.54% 2/367 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Stress cardiomyopathy	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Ventricular extrasystoles	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Cardiac disorders Ventricular tachycardia	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Congenital, familial and genetic disorders Myocardial bridging	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Ear and labyrinth disorders Vertigo	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Endocrine disorders Hyperthyroidism	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Abdominal pain upper	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Acute abdomen	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Ascites	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Colitis	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Colitis ischaemic	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Diabetic gastroparesis	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Diarrhoea	0.55% 2/364 • Number of events 3 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.54% 2/367 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Haematochezia	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Incarcerated inguinal hernia	0.27% 1/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Inguinal hernia	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Intestinal ischaemia	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Intestinal obstruction	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Large intestine polyp	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Melaena	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Nausea	0.27% 1/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Obstructive pancreatitis	0.55% 2/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Oesophageal haemorrhage	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Pancreatitis acute	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Hepatobiliary disorders Cholelithiasis	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Hepatobiliary disorders Hepatitis acute	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Immune system disorders Anaphylactic shock	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Abdominal abscess	0.55% 2/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Abdominal sepsis	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Appendicitis	0.55% 2/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Aspergillus infection	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Cellulitis	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	1.6% 6/367 • Number of events 7 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Covid-19	0.55% 2/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Covid-19 pneumonia	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Cystitis	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Dengue fever	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Device related infection	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Diverticulitis	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Erysipelas	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.54% 2/367 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Gastroenteritis	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Hepatitis b	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Influenza	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Osteomyelitis	0.55% 2/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Pneumonia	1.4% 5/364 • Number of events 5 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	1.6% 6/367 • Number of events 6 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Pneumonia viral	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Postoperative wound infection	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Pyelonephritis	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Pyelonephritis acute	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Sepsis	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.54% 2/367 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Septic encephalopathy	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Septic shock	0.82% 3/364 • Number of events 5 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	1.1% 4/367 • Number of events 4 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Soft tissue infection	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Tooth abscess	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Urinary tract infection	1.4% 5/364 • Number of events 5 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Urosepsis	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Injury, poisoning and procedural complications Concussion	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Injury, poisoning and procedural complications Contusion	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Injury, poisoning and procedural complications Craniocerebral injury	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Injury, poisoning and procedural complications Fall	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.54% 2/367 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Injury, poisoning and procedural complications Humerus fracture	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Injury, poisoning and procedural complications Postoperative respiratory failure	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Injury, poisoning and procedural complications Rib fracture	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Injury, poisoning and procedural complications Spinal fracture	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Injury, poisoning and procedural complications Subdural haemorrhage	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Injury, poisoning and procedural complications Toxicity to various agents	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Metabolism and nutrition disorders Dehydration	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Metabolism and nutrition disorders Hyperglycaemic hyperosmolar nonketotic syndrome	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Metabolism and nutrition disorders Hypoglycaemia	0.55% 2/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Musculoskeletal and connective tissue disorders Foot deformity	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.27% 1/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Biliary neoplasm	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal carcinoma	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive breast carcinoma	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian adenoma	0.50% 1/200 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/193 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary renal cell carcinoma	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasmacytoma	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/164 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.57% 1/174 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostatic adenoma	0.00% 0/164 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.57% 1/174 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tonsil cancer	0.27% 1/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/200 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.52% 1/193 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Nervous system disorders Altered state of consciousness	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Nervous system disorders Basal ganglia haemorrhage	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Nervous system disorders Cerebrovascular accident	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Nervous system disorders Epilepsy	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Nervous system disorders Generalised tonic-clonic seizure	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Nervous system disorders Intracranial aneurysm	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Nervous system disorders Ischaemic stroke	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Nervous system disorders Presyncope	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Nervous system disorders Seizure	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Nervous system disorders Subarachnoid haemorrhage	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Nervous system disorders Syncope	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Nervous system disorders Thrombotic cerebral infarction	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Nervous system disorders Transient ischaemic attack	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Product Issues Prosthetic cardiac valve malfunction	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Renal and urinary disorders Acute kidney injury	1.4% 5/364 • Number of events 5 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.82% 3/367 • Number of events 3 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Renal and urinary disorders Bladder stenosis	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Renal and urinary disorders Calculus bladder	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Renal and urinary disorders Calculus urinary	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Renal and urinary disorders Chronic kidney disease	0.82% 3/364 • Number of events 3 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.54% 2/367 • Number of events 3 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Renal and urinary disorders Hypertensive nephropathy	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Renal and urinary disorders Hypertonic bladder	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Renal and urinary disorders Renal failure	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.54% 2/367 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Renal and urinary disorders Renal impairment	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.54% 2/367 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Renal and urinary disorders Ureterolithiasis	0.55% 2/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Renal and urinary disorders Urinary bladder haemorrhage	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Renal and urinary disorders Urinary retention	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.55% 2/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.54% 2/367 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Respiratory, thoracic and mediastinal disorders Malignant pleural effusion	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Respiratory, thoracic and mediastinal disorders Tracheomalacia	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Surgical and medical procedures Cardiac device implantation	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Surgical and medical procedures Coronary angioplasty	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Surgical and medical procedures Percutaneous coronary intervention	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Vascular disorders Aortic aneurysm	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Vascular disorders Aortic stenosis	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Vascular disorders Bleeding varicose vein	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Vascular disorders Deep vein thrombosis	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Vascular disorders Distributive shock	0.55% 2/364 • Number of events 2 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Vascular disorders Hypertension	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Vascular disorders Hypotension	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Vascular disorders Hypovolaemic shock	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Vascular disorders Orthostatic hypotension	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/364 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.27% 1/367 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Vascular disorders Peripheral ischaemia	0.27% 1/364 • Number of events 1 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	0.00% 0/367 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.

Other adverse events

Measure	Tirzepatide - MTD n=364 participants at risk Participants received a starting dose of 2.5 mg tirzepatide administered SC QW and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or MTD tolerated by the participant (5 mg QW or 10 mg QW).	Placebo n=367 participants at risk Participants received placebo administered SC QW.
Cardiac disorders Cardiac failure	3.0% 11/364 • Number of events 19 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	5.4% 20/367 • Number of events 24 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Abdominal pain upper	5.2% 19/364 • Number of events 24 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	1.9% 7/367 • Number of events 10 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Constipation	14.8% 54/364 • Number of events 78 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	6.0% 22/367 • Number of events 27 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Diarrhoea	17.9% 65/364 • Number of events 185 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	6.3% 23/367 • Number of events 33 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Dyspepsia	6.3% 23/364 • Number of events 30 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	2.2% 8/367 • Number of events 11 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Nausea	17.0% 62/364 • Number of events 214 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	6.3% 23/367 • Number of events 32 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Gastrointestinal disorders Vomiting	10.4% 38/364 • Number of events 71 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	1.9% 7/367 • Number of events 9 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Covid-19	9.1% 33/364 • Number of events 35 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	11.2% 41/367 • Number of events 45 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Infections and infestations Urinary tract infection	8.5% 31/364 • Number of events 42 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	6.0% 22/367 • Number of events 25 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Metabolism and nutrition disorders Decreased appetite	10.4% 38/364 • Number of events 42 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	1.6% 6/367 • Number of events 7 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Nervous system disorders Dizziness	9.3% 34/364 • Number of events 81 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	4.9% 18/367 • Number of events 20 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.
Vascular disorders Hypotension	6.0% 22/364 • Number of events 25 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.	2.7% 10/367 • Number of events 10 • Baseline Up To 162 Weeks All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Based on the planned safety analysis, adverse event analysis was planned as per the treatment regimen received.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: ClinicalTrials.gov@lilly.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60