Trial Outcomes & Findings for Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events (NCT NCT01730534)

Participant milestones
Measure	Dapa 10 mg Dapagliflozin 10 mg tablets administered orally once daily	Placebo Matching placebo for dapagliflozin 10 mg administered orally once daily
Overall Study STARTED	8582	8578
Overall Study COMPLETED	8473	8433
Overall Study NOT COMPLETED	109	145

Reasons for withdrawal
Measure	Dapa 10 mg Dapagliflozin 10 mg tablets administered orally once daily	Placebo Matching placebo for dapagliflozin 10 mg administered orally once daily
Overall Study Withdrawal by Subject	97	127
Overall Study Lost to Follow-up	12	18

Baseline characteristics by cohort
Measure	Dapa 10 mg n=8582 Participants Dapagliflozin 10 mg tablets administered orally once daily	Placebo n=8578 Participants Matching placebo for dapagliflozin 10 mg administered orally once daily	Total n=17160 Participants Total of all reporting groups
Age, Continuous	63.9 years STANDARD_DEVIATION 6.8 • n=5 Participants	64.0 years STANDARD_DEVIATION 6.8 • n=7 Participants	63.9 years STANDARD_DEVIATION 6.8 • n=5 Participants
Age, Customized <65 years	4631 Participants n=5 Participants	4622 Participants n=7 Participants	9253 Participants n=5 Participants
Age, Customized >=65 years	3951 Participants n=5 Participants	3956 Participants n=7 Participants	7907 Participants n=5 Participants
Age, Customized <75 years	8044 Participants n=5 Participants	8020 Participants n=7 Participants	16064 Participants n=5 Participants
Age, Customized >=75 years	538 Participants n=5 Participants	558 Participants n=7 Participants	1096 Participants n=5 Participants
Sex: Female, Male Female	3171 Participants n=5 Participants	3251 Participants n=7 Participants	6422 Participants n=5 Participants
Sex: Female, Male Male	5411 Participants n=5 Participants	5327 Participants n=7 Participants	10738 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1298 Participants n=5 Participants	1270 Participants n=7 Participants	2568 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7284 Participants n=5 Participants	7308 Participants n=7 Participants	14592 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	6843 Participants n=5 Participants	6810 Participants n=7 Participants	13653 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	295 Participants n=5 Participants	308 Participants n=7 Participants	603 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1148 Participants n=5 Participants	1155 Participants n=7 Participants	2303 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	52 Participants n=5 Participants	52 Participants n=7 Participants	104 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	9 Participants n=5 Participants	13 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized Other	235 Participants n=5 Participants	240 Participants n=7 Participants	475 Participants n=5 Participants
Baseline CV risk category Established CV disease	3474 Participants n=5 Participants	3500 Participants n=7 Participants	6974 Participants n=5 Participants
Baseline CV risk category Multiple risk factors for CV events	5108 Participants n=5 Participants	5078 Participants n=7 Participants	10186 Participants n=5 Participants

Outcome measures
Measure	Dapa 10 mg n=8582 Participants Dapagliflozin 10 mg tablets administered orally once daily	Placebo n=8578 Participants Matching placebo for dapagliflozin 10 mg administered orally once daily
Subjects Included in the Composite Endpoint of CV Death, MI or Ischemic Stroke Number of patients with an event	756 Participants	803 Participants

Outcome measures
Measure	Dapa 10 mg n=8582 Participants Dapagliflozin 10 mg tablets administered orally once daily	Placebo n=8578 Participants Matching placebo for dapagliflozin 10 mg administered orally once daily
Subjects Included in the Composite Endpoint of CV Death or Hospitalization Due to Heart Failure. Number of patients with an event	417 Participants	496 Participants

Outcome measures
Measure	Dapa 10 mg n=8582 Participants Dapagliflozin 10 mg tablets administered orally once daily	Placebo n=8578 Participants Matching placebo for dapagliflozin 10 mg administered orally once daily
Subjects Included in the Renal Composite Endpoint: Confirmed Sustained ≥40% Decrease in eGFR to eGFR <60 ml/Min/1.73m2 and/or ESRD and/or Renal or CV Death. Number of patients with an event	370 Participants	480 Participants

Outcome measures
Measure	Dapa 10 mg n=8582 Participants Dapagliflozin 10 mg tablets administered orally once daily	Placebo n=8578 Participants Matching placebo for dapagliflozin 10 mg administered orally once daily
Subjects Included in the Endpoint of All-cause Mortality. Number of patients with an event	529 Participants	570 Participants

Blood and lymphatic system disorders

Agranulocytosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Anaemia

0.23%

20/8574 • Number of events 20 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.33%

28/8569 • Number of events 30 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Anaemia of chronic disease

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Anaemia vitamin b12 deficiency

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Coagulopathy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Disseminated intravascular coagulation

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Elephantiasis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Febrile neutropenia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Haemorrhagic anaemia

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Hilar lymphadenopathy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Immune thrombocytopenic purpura

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Iron deficiency anaemia

0.14%

12/8574 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.21%

18/8569 • Number of events 18 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Leukocytosis

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Lymphadenopathy

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Lymphadenopathy mediastinal

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Microcytic anaemia

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Neutropenia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Normocytic anaemia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Pancytopenia

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Plasmacytosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Splenic cyst

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Splenic infarction

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Thrombocytopenia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Blood and lymphatic system disorders

Thrombocytopenic purpura

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Acute cardiac event

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Acute coronary syndrome

0.20%

17/8574 • Number of events 22 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.36%

31/8569 • Number of events 33 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Acute left ventricular failure

0.19%

16/8574 • Number of events 22 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.20%

17/8569 • Number of events 23 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Acute myocardial infarction

3.1%

265/8574 • Number of events 293 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

2.7%

233/8569 • Number of events 264 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Adams-stokes syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Angina pectoris

1.8%

154/8574 • Number of events 178 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

1.9%

159/8569 • Number of events 175 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Angina unstable

3.2%

271/8574 • Number of events 349 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

3.1%

269/8569 • Number of events 332 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Aortic valve calcification

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Aortic valve disease

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Aortic valve disease mixed

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Aortic valve incompetence

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Aortic valve stenosis

0.12%

10/8574 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Arrhythmia

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Arteriosclerosis coronary artery

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.19%

16/8569 • Number of events 21 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Atrial fibrillation

1.4%

117/8574 • Number of events 138 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

1.6%

139/8569 • Number of events 177 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Atrial flutter

0.24%

21/8574 • Number of events 25 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.40%

34/8569 • Number of events 44 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Atrial tachycardia

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Atrial thrombosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Atrioventricular block

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Atrioventricular block complete

0.22%

19/8574 • Number of events 19 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.16%

14/8569 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Atrioventricular block second degree

0.12%

10/8574 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Bifascicular block

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Bradyarrhythmia

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Bradycardia

0.19%

16/8574 • Number of events 17 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.25%

21/8569 • Number of events 22 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Bundle branch block left

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Bundle branch block right

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardiac arrest

0.38%

33/8574 • Number of events 34 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.36%

31/8569 • Number of events 32 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardiac asthma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardiac disorder

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardiac failure

1.7%

147/8574 • Number of events 199 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

2.2%

188/8569 • Number of events 252 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardiac failure acute

0.26%

22/8574 • Number of events 25 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.36%

31/8569 • Number of events 39 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardiac failure chronic

0.14%

12/8574 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.23%

20/8569 • Number of events 23 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardiac failure congestive

1.4%

121/8574 • Number of events 177 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

1.7%

147/8569 • Number of events 205 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardiac tamponade

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardiac ventricular thrombosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardio-respiratory arrest

0.14%

12/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.13%

11/8569 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardiogenic shock

0.22%

19/8574 • Number of events 19 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.15%

13/8569 • Number of events 16 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardiomegaly

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardiomyopathy

0.08%

7/8574 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardiomyopathy acute

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardiopulmonary failure

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardiovascular disorder

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cardiovascular insufficiency

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Chronic left ventricular failure

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Chronotropic incompetence

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Conduction disorder

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Congestive cardiomyopathy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Cor pulmonale

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Coronary artery aneurysm

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Coronary artery disease

1.2%

106/8574 • Number of events 113 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.98%

84/8569 • Number of events 87 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Coronary artery occlusion

0.10%

9/8574 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Coronary artery stenosis

0.14%

12/8574 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.26%

22/8569 • Number of events 23 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Coronary artery thrombosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Coronary ostial stenosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Diastolic dysfunction

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Dressler's syndrome

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Extrasystoles

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Heart valve incompetence

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Heart valve stenosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Hypertensive heart disease

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Ischaemic cardiomyopathy

0.12%

10/8574 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.21%

18/8569 • Number of events 18 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Left ventricular dysfunction

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Left ventricular failure

0.13%

11/8574 • Number of events 15 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.15%

13/8569 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Mitral valve incompetence

0.08%

7/8574 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Mitral valve stenosis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Myocardial infarction

1.1%

96/8574 • Number of events 104 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

1.3%

108/8569 • Number of events 111 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Myocardial ischaemia

0.55%

47/8574 • Number of events 49 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.63%

54/8569 • Number of events 61 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Myocarditis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Nodal arrhythmia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Palpitations

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Pericardial effusion

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Pericarditis

0.09%

8/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Postinfarction angina

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Prinzmetal angina

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Pulseless electrical activity

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Rheumatic heart disease

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Right ventricular failure

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Sinus arrest

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Sinus bradycardia

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Sinus node dysfunction

0.16%

14/8574 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.15%

13/8569 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Sinus tachycardia

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Supraventricular tachycardia

0.14%

12/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Tachyarrhythmia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Tachycardia

0.06%

5/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Torsade de pointes

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Tricuspid valve incompetence

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Trifascicular block

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Ventricular arrhythmia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Ventricular extrasystoles

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Ventricular failure

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Ventricular fibrillation

0.09%

8/8574 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Cardiac disorders

Ventricular tachycardia

0.22%

19/8574 • Number of events 23 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.18%

15/8569 • Number of events 21 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Congenital, familial and genetic disorders

Adenomatous polyposis coli

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Congenital, familial and genetic disorders

Congenital hepatobiliary anomaly

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Congenital, familial and genetic disorders

Diverticulitis meckel's

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Congenital, familial and genetic disorders

Heart disease congenital

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Congenital, familial and genetic disorders

Hydrocele

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Congenital, familial and genetic disorders

Hypertrophic cardiomyopathy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Congenital, familial and genetic disorders

Vitello-intestinal duct remnant

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Ear and labyrinth disorders

Acute vestibular syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Ear and labyrinth disorders

Deafness neurosensory

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Ear and labyrinth disorders

Hypoacusis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Ear and labyrinth disorders

Sudden hearing loss

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Ear and labyrinth disorders

Tinnitus

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Ear and labyrinth disorders

Vertigo

0.13%

11/8574 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.14%

12/8569 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Ear and labyrinth disorders

Vertigo labyrinthine

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Ear and labyrinth disorders

Vertigo positional

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Ear and labyrinth disorders

Vestibular ataxia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Ear and labyrinth disorders

Vestibular disorder

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Endocrine disorders

Adrenal insufficiency

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Endocrine disorders

Adrenal mass

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Endocrine disorders

Adrenomegaly

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Endocrine disorders

Basedow's disease

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Endocrine disorders

Goitre

0.08%

7/8574 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Endocrine disorders

Hyperadrenalism

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Endocrine disorders

Hyperparathyroidism

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Endocrine disorders

Hyperparathyroidism primary

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Endocrine disorders

Hypopituitarism

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Endocrine disorders

Thyroid mass

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Endocrine disorders

Toxic nodular goitre

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Amaurosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Amaurosis fugax

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Amblyopia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Astigmatism

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Blindness transient

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Cataract

0.33%

28/8574 • Number of events 31 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.30%

26/8569 • Number of events 32 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Cataract nuclear

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Cataract subcapsular

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Corneal deposits

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Dacryostenosis acquired

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Diabetic retinal oedema

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Diabetic retinopathy

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Diplopia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Endocrine ophthalmopathy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Exophthalmos

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Eye haemorrhage

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Glaucoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Iridocyclitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Iritis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Lagophthalmos

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Macular degeneration

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Macular fibrosis

0.02%

2/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Macular oedema

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Maculopathy

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Retinal artery occlusion

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Retinal detachment

0.02%

2/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Retinal haemorrhage

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Retinal tear

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Retinal vascular occlusion

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Retinal vein occlusion

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Tolosa-hunt syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Tractional retinal detachment

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Ulcerative keratitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Vision blurred

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Visual impairment

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Eye disorders

Vitreous haemorrhage

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Abdominal adhesions

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Abdominal discomfort

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Abdominal hernia

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Abdominal hernia obstructive

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Abdominal incarcerated hernia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Abdominal pain

0.15%

13/8574 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Abdominal pain lower

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Abdominal pain upper

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Acute haemorrhagic ulcerative colitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Alcoholic pancreatitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Anal fissure

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Anal fistula

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Ascites

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Barrett's oesophagus

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Colitis

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.13%

11/8569 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Colitis ischaemic

0.08%

7/8574 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Colitis microscopic

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Colitis ulcerative

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Constipation

0.15%

13/8574 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Diabetic gastroenteropathy

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Diabetic gastroparesis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Diarrhoea

0.12%

10/8574 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.13%

11/8569 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Dieulafoy's vascular malformation

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Diverticulum

0.06%

5/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Diverticulum intestinal haemorrhagic

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Duodenal ulcer

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Duodenal ulcer haemorrhage

0.05%

4/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Duodenal ulcer perforation

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Duodenitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Dyspepsia

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Dysphagia

0.06%

5/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Enteritis

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Enterocolitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Enterocutaneous fistula

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Enterovesical fistula

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Epigastric discomfort

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Epiploic appendagitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Faecaloma

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Faeces discoloured

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Food poisoning

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastric haemorrhage

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastric perforation

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastric polyps

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastric stenosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastric ulcer

0.10%

9/8574 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.13%

11/8569 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastric ulcer haemorrhage

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastritis

0.15%

13/8574 • Number of events 15 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.23%

20/8569 • Number of events 20 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastritis erosive

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastroduodenitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastrointestinal angiodysplasia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastrointestinal haemorrhage

0.20%

17/8574 • Number of events 18 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.21%

18/8569 • Number of events 18 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastrointestinal inflammation

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastrointestinal necrosis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastrointestinal obstruction

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastrointestinal perforation

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastrointestinal ulcer haemorrhage

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gastrooesophageal reflux disease

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.12%

10/8569 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Gingival bleeding

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Haematemesis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Haematochezia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Haemorrhoidal haemorrhage

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Haemorrhoids

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Hernial eventration

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Hiatus hernia

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Ileus

0.02%

2/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Ileus paralytic

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Impaired gastric emptying

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Incarcerated umbilical hernia

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Inguinal hernia

0.12%

10/8574 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.15%

13/8569 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Intestinal fibrosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Intestinal haemorrhage

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Intestinal infarction

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Intestinal ischaemia

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Intestinal obstruction

0.03%

3/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Intestinal perforation

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Intestinal polyp

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Intestinal pseudo-obstruction

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Intra-abdominal fluid collection

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Intra-abdominal haemorrhage

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Intussusception

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Jejunal perforation

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Large intestinal ulcer

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Large intestinal ulcer haemorrhage

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Large intestine perforation

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Large intestine polyp

0.14%

12/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Lower gastrointestinal haemorrhage

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Lumbar hernia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Mallory-weiss syndrome

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Melaena

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Mesenteric artery embolism

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Mesenteric artery stenosis

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Mesenteric panniculitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Mesenteric vascular insufficiency

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Nausea

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Obstruction gastric

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Obstructive pancreatitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Odynophagia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Oesophageal food impaction

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Oesophageal obstruction

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Oesophageal perforation

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Oesophageal ulcer

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Oesophageal varices haemorrhage

0.02%

2/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Oesophagitis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Oesophagitis ulcerative

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Palatal oedema

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Pancreatic cyst

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Pancreatic duct obstruction

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Pancreatic necrosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Pancreatic pseudocyst

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Pancreatitis

0.14%

12/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.14%

12/8569 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Pancreatitis acute

0.15%

13/8574 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.18%

15/8569 • Number of events 17 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Pancreatitis chronic

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Pancreatitis necrotising

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Pancreatitis relapsing

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Pancreatolithiasis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Peptic ulcer

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Peptic ulcer haemorrhage

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Periodontal disease

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Peritoneal adhesions

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Pneumoperitoneum

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Portal hypertensive gastropathy

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Proctitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Rectal haemorrhage

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Retroperitoneal haematoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Retroperitoneal haemorrhage

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Salivary gland cyst

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Small intestinal haemorrhage

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Small intestinal obstruction

0.12%

10/8574 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Small intestinal perforation

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Small intestine ulcer

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Steatorrhoea

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Thrombosis mesenteric vessel

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Umbilical hernia

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Upper gastrointestinal haemorrhage

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Varices oesophageal

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Gastrointestinal disorders

Vomiting

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Adverse drug reaction

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Asthenia

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.12%

10/8569 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Cardiac death

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Chest pain

0.34%

29/8574 • Number of events 34 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.23%

20/8569 • Number of events 20 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Complication associated with device

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Critical illness

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Death

0.94%

81/8574 • Number of events 81 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

1.0%

89/8569 • Number of events 89 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Dehiscence

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Drowning

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Drug intolerance

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Drug withdrawal syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Exercise tolerance decreased

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Gait disturbance

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

General physical health deterioration

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Generalised oedema

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Granuloma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Hernia

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Hypothermia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Impaired healing

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Implant site inflammation

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Incarcerated hernia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Inflammation

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Malaise

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Medical device pain

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Medical device site irritation

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Microlithiasis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Multiple organ dysfunction syndrome

0.10%

9/8574 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Necrobiosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Necrosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Non-cardiac chest pain

1.1%

93/8574 • Number of events 110 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

1.2%

107/8569 • Number of events 120 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Oedema

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Oedema peripheral

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Organ failure

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Pacemaker syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Pain

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Pelvic mass

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Peripheral swelling

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Pyrexia

0.08%

7/8574 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.15%

13/8569 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Soft tissue inflammation

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Stent-graft endoleak

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Submandibular mass

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Sudden cardiac death

0.16%

14/8574 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.19%

16/8569 • Number of events 16 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Sudden death

0.24%

21/8574 • Number of events 21 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.27%

23/8569 • Number of events 23 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Systemic inflammatory response syndrome

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Vascular stent occlusion

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Vascular stent stenosis

0.08%

7/8574 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

General disorders

Vascular stent thrombosis

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Bile duct obstruction

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Bile duct stenosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Bile duct stone

0.10%

9/8574 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Biliary colic

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Biliary dyskinesia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Biliary dyspepsia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Cholangitis

0.13%

11/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Cholangitis acute

0.05%

4/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Cholecystitis

0.21%

18/8574 • Number of events 18 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.26%

22/8569 • Number of events 23 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Cholecystitis acute

0.29%

25/8574 • Number of events 25 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.26%

22/8569 • Number of events 22 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Cholecystitis chronic

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Cholelithiasis

0.30%

26/8574 • Number of events 26 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.44%

38/8569 • Number of events 40 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Chronic hepatic failure

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Drug-induced liver injury

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Gallbladder cholesterolosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Gallbladder perforation

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Gallbladder polyp

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Hepatic cirrhosis

0.08%

7/8574 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.13%

11/8569 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Hepatic cyst

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Hepatic failure

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Hepatic fibrosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Hepatic mass

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Hepatic steatosis

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Hepatitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Hepatitis acute

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Hepatorenal syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Hydrocholecystis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Ischaemic hepatitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Jaundice

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Liver injury

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Non-alcoholic steatohepatitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Porcelain gallbladder

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Hepatobiliary disorders

Portal vein thrombosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Immune system disorders

Allergy to metals

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Immune system disorders

Allergy to vaccine

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Immune system disorders

Anaphylactic reaction

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Immune system disorders

Anaphylactic shock

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Immune system disorders

Drug hypersensitivity

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Immune system disorders

Hashitoxicosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Immune system disorders

Hypersensitivity

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Immune system disorders

Sarcoidosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Abdominal abscess

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Abdominal sepsis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Abdominal wall abscess

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Abscess

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Abscess limb

0.09%

8/8574 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Acquired immunodeficiency syndrome

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Acute endocarditis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Acute hepatitis b

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Acute sinusitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Amoebiasis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Anal abscess

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Appendiceal abscess

0.01%

1/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Appendicitis

0.14%

12/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.14%

12/8569 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Appendicitis perforated

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Arthritis bacterial

0.07%

6/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.13%

11/8569 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Arthritis infective

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Aspergilloma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Atypical pneumonia

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Bacteraemia

0.07%

6/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Bacterascites

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Bacterial colitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Bacterial sepsis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Bacterial tracheitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Bacteriuria

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Beta haemolytic streptococcal infection

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Biliary sepsis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Bone abscess

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Brain abscess

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Breast abscess

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Bronchitis

0.17%

15/8574 • Number of events 16 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.41%

35/8569 • Number of events 35 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Bronchitis bacterial

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Bronchitis viral

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Burn infection

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Bursitis infective

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Campylobacter gastroenteritis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Cellulitis

0.98%

84/8574 • Number of events 100 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

1.1%

93/8569 • Number of events 117 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Cellulitis gangrenous

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Cellulitis of male external genital organ

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Cellulitis orbital

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Cellulitis staphylococcal

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Central nervous system infection

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Chest wall abscess

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Cholecystitis infective

0.07%

6/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Chronic hepatitis c

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Chronic sinusitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Clostridial sepsis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Clostridium difficile colitis

0.08%

7/8574 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Clostridium difficile infection

0.05%

4/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Cystitis

0.10%

9/8574 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Cytomegalovirus viraemia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Dengue fever

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Device related infection

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Diabetic foot infection

0.12%

10/8574 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.15%

13/8569 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Diabetic gangrene

0.08%

7/8574 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.13%

11/8569 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Diarrhoea infectious

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Diverticulitis

0.23%

20/8574 • Number of events 24 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.23%

20/8569 • Number of events 22 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Diverticulitis intestinal haemorrhagic

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Empyema

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Encephalitis

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Encephalomyelitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Endocarditis

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Endocarditis bacterial

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Endocarditis enterococcal

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Endocarditis staphylococcal

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Endometritis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Enteritis infectious

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Enterococcal bacteraemia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Enterococcal sepsis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Epididymitis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Epiglottitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Erysipelas

0.13%

11/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.15%

13/8569 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Escherichia bacteraemia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Escherichia sepsis

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Escherichia urinary tract infection

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

External ear cellulitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Extradural abscess

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Fungal infection

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Gangrene

0.26%

22/8574 • Number of events 23 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.35%

30/8569 • Number of events 40 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Gas gangrene

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Gastric infection

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Gastroenteritis

0.30%

26/8574 • Number of events 27 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.32%

27/8569 • Number of events 27 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Gastroenteritis norovirus

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Gastroenteritis rotavirus

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Gastroenteritis salmonella

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Gastroenteritis viral

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Giardiasis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Groin abscess

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

H1n1 influenza

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Hiv infection

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Hiv-associated neurocognitive disorder

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Haematoma infection

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Helicobacter infection

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Hepatitis a

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Hepatitis b

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Hepatitis e

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Hepatitis viral

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Herpes zoster

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Human anaplasmosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Implant site infection

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Infected skin ulcer

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Infection

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Infectious colitis

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Infective exacerbation of chronic obstructive airways disease

0.03%

3/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Infective gastroduodenitis

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Influenza

0.20%

17/8574 • Number of events 17 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.18%

15/8569 • Number of events 15 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Intervertebral discitis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Klebsiella bacteraemia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Klebsiella sepsis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Legionella infection

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Liver abscess

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Localised infection

0.19%

16/8574 • Number of events 16 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.12%

10/8569 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Lower respiratory tract infection

0.10%

9/8574 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.12%

10/8569 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Lung abscess

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Lung infection

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Lyme disease

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Malaria

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Mastitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Mastoiditis

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Mediastinitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Medical device site abscess

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Medical device site infection

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Medical device site joint infection

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Meningitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Meningitis aseptic

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Meningitis pneumococcal

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Meningitis viral

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Mucormycosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Muscle abscess

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Necrotising fasciitis

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Neurosyphilis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Neutropenic sepsis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Oesophageal candidiasis

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Onychomycosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Oral candidiasis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Orchitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Oropharyngeal candidiasis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Osteomyelitis

0.30%

26/8574 • Number of events 35 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.46%

39/8569 • Number of events 46 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Osteomyelitis acute

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Osteomyelitis chronic

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Otitis externa

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Otitis media

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Otitis media chronic

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pancreatic abscess

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Parainfluenzae virus infection

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Parotitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pelvic abscess

0.02%

2/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pelvic inflammatory disease

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Perineal abscess

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Perinephric abscess

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Periodontitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Peritonitis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Peritonitis bacterial

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Peritonsillar abscess

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pharyngitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pleurisy viral

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pneumococcal infection

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pneumococcal sepsis

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pneumonia

2.3%

194/8574 • Number of events 212 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

2.6%

219/8569 • Number of events 246 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pneumonia bacterial

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pneumonia pneumococcal

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pneumonia respiratory syncytial viral

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pneumonia staphylococcal

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pneumonia streptococcal

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pneumonia viral

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Post procedural cellulitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Post procedural infection

0.10%

9/8574 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Postoperative abscess

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Postoperative wound infection

0.13%

11/8574 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.15%

13/8569 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Prostatic abscess

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pulmonary sepsis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pulmonary tuberculosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pyelitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pyelonephritis

0.16%

14/8574 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.16%

14/8569 • Number of events 15 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pyelonephritis acute

0.12%

10/8574 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.18%

15/8569 • Number of events 15 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Pyelonephritis chronic

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Rectal abscess

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Renal abscess

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Respiratory syncytial virus bronchiolitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Respiratory syncytial virus bronchitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Respiratory syncytial virus infection

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Respiratory tract infection

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Retroperitoneal abscess

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Rhinitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Rickettsiosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Rotavirus infection

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Salmonella bacteraemia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Scrotal abscess

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Scrub typhus

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Sepsis

0.90%

77/8574 • Number of events 84 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.82%

70/8569 • Number of events 71 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Sepsis syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Septic arthritis staphylococcal

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Septic shock

0.24%

21/8574 • Number of events 22 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.28%

24/8569 • Number of events 27 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Sinusitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Sinusitis fungal

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Skin bacterial infection

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Skin infection

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Soft tissue infection

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Splenic abscess

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Staphylococcal abscess

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Staphylococcal bacteraemia

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Staphylococcal infection

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Staphylococcal sepsis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Streptococcal abscess

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Streptococcal bacteraemia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Streptococcal sepsis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Tick-borne fever

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Tonsillitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Tooth abscess

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Tooth infection

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Tracheitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Tracheobronchitis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Tuberculosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Upper respiratory tract infection

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Urinary tract infection

0.57%

49/8574 • Number of events 53 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.78%

67/8569 • Number of events 71 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Urinary tract infection bacterial

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Urinary tract infection enterococcal

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Urosepsis

0.26%

22/8574 • Number of events 23 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.29%

25/8569 • Number of events 26 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Vestibular neuronitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Viraemia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Viral infection

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Viral myocarditis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Viral sinusitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Viral upper respiratory tract infection

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

West nile viral infection

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Wound abscess

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Wound infection

0.13%

11/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.12%

10/8569 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Infections and infestations

Wound infection pseudomonas

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Abdominal injury

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Abdominal wall wound

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Abdominal wound dehiscence

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Accidental overdose

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Accidental poisoning

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Acetabulum fracture

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Alcohol poisoning

0.02%

2/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Allergic transfusion reaction

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Anaemia postoperative

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Anastomotic leak

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Anastomotic ulcer

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Ankle fracture

0.22%

19/8574 • Number of events 19 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.16%

14/8569 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Arterial bypass occlusion

0.02%

2/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Arterial injury

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Arterial restenosis

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Avulsion fracture

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Back injury

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Bone contusion

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Brain contusion

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Burns second degree

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Cardiac procedure complication

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Cardiac valve replacement complication

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Carotid artery restenosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Cartilage injury

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Cataract operation complication

0.01%

1/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Cement embolism

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Cervical vertebral fracture

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Chest crushing

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Chest injury

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Clavicle fracture

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Complications of transplanted liver

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Compression fracture

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Concussion

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Confusion postoperative

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Contusion

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Coronary artery restenosis

0.02%

2/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Coronary bypass stenosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Costal cartilage fracture

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Craniocerebral injury

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Cystitis radiation

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Exposure to toxic agent

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Extradural haematoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Eyelid injury

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Facial bones fracture

0.12%

10/8574 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Fall

0.16%

14/8574 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.23%

20/8569 • Number of events 20 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Femoral neck fracture

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Femur fracture

0.19%

16/8574 • Number of events 16 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.21%

18/8569 • Number of events 18 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Fibula fracture

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Foot fracture

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Foreign body in gastrointestinal tract

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Foreign body in respiratory tract

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Fracture displacement

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Fractured sacrum

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Gun shot wound

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Haematuria traumatic

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Hand fracture

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Head injury

0.05%

4/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Heat stroke

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Hip fracture

0.15%

13/8574 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.18%

15/8569 • Number of events 16 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Humerus fracture

0.13%

11/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.23%

20/8569 • Number of events 20 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Ilium fracture

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Incisional hernia

0.07%

6/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Injury

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Intentional overdose

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Jaw fracture

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Joint dislocation

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Joint injury

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Laceration

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Ligament rupture

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Ligament sprain

0.02%

2/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Limb crushing injury

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Limb fracture

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Limb injury

0.08%

7/8574 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Limb traumatic amputation

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Lisfranc fracture

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Lower limb fracture

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Lumbar vertebral fracture

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Meniscus injury

0.07%

6/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Multiple fractures

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Multiple injuries

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Muscle rupture

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Muscle strain

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Nerve injury

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Ocular procedural complication

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Overdose

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Patella fracture

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Pelvic fracture

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Periorbital haematoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Peripheral artery restenosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Periprocedural myocardial infarction

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Periprosthetic fracture

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Pneumoconiosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Pneumothorax traumatic

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Post concussion syndrome

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Post laminectomy syndrome

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Post procedural complication

0.09%

8/8574 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.16%

14/8569 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Post procedural constipation

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Post procedural discharge

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Post procedural haematoma

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Post procedural haematuria

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Post procedural haemorrhage

0.13%

11/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Post procedural inflammation

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Post procedural myocardial infarction

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Postoperative delirium

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Postoperative ileus

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Postoperative respiratory failure

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Postoperative thoracic procedure complication

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Postoperative thrombosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Postoperative wound complication

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Procedural complication

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Procedural haemorrhage

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Procedural pain

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Procedural pneumothorax

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Procedural shock

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Pubis fracture

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Radiation oesophagitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Radius fracture

0.08%

7/8574 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.12%

10/8569 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Rectal laceration postoperative

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Rib fracture

0.14%

12/8574 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.18%

15/8569 • Number of events 17 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Road traffic accident

0.09%

8/8574 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Sedation complication

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Seroma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Skin abrasion

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Skin injury

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Skin wound

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Skull fracture

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Skull fractured base

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Soft tissue injury

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Spinal column injury

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Spinal compression fracture

0.14%

12/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Spinal fracture

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Splenic injury

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Splenic rupture

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Stab wound

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Sternal fracture

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Stoma site haemorrhage

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Subarachnoid haemorrhage

0.07%

6/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Subcutaneous haematoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Subdural haematoma

0.09%

8/8574 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.13%

11/8569 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Subdural haemorrhage

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Tendon injury

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Tendon rupture

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Thermal burn

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Thoracic vertebral fracture

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Tibia fracture

0.14%

12/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Tongue injury

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Toxicity to various agents

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Transfusion reaction

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Transplant dysfunction

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Traumatic arthritis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Traumatic fracture

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Traumatic haemothorax

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Traumatic intracranial haemorrhage

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Ulna fracture

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Upper limb fracture

0.09%

8/8574 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Vascular graft occlusion

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Vascular graft restenosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Vascular graft thrombosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Vascular pseudoaneurysm

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Wound

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Wound dehiscence

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Wound haematoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Wound necrosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Injury, poisoning and procedural complications

Wrist fracture

0.07%

6/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Anticoagulation drug level below therapeutic

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Blood creatine phosphokinase increased

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Blood creatinine increased

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Blood glucose abnormal

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Blood glucose increased

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Blood pressure decreased

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Blood pressure increased

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Brain natriuretic peptide increased

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Catheterisation cardiac

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Electrocardiogram qt prolonged

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Electrocardiogram st segment elevation

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

General physical condition abnormal

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Glomerular filtration rate decreased

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Hepatic enzyme increased

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Hepatitis c antibody positive

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

International normalised ratio increased

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Liver function test increased

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Transaminases increased

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Troponin i increased

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Troponin t increased

0.02%

2/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Troponin increased

0.13%

11/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Urine cytology abnormal

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Investigations

Weight decreased

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Adult failure to thrive

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Alcoholic ketoacidosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Decreased appetite

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Dehydration

0.23%

20/8574 • Number of events 21 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.22%

19/8569 • Number of events 19 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Diabetes mellitus

0.06%

5/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.15%

13/8569 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Diabetes mellitus inadequate control

0.16%

14/8574 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.34%

29/8569 • Number of events 34 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Diabetes with hyperosmolarity

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Diabetic complication

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Diabetic ketoacidosis

0.31%

27/8574 • Number of events 29 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.27%

23/8569 • Number of events 27 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Diabetic ketosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Diabetic metabolic decompensation

0.20%

17/8574 • Number of events 23 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.32%

27/8569 • Number of events 35 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Electrolyte imbalance

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Euglycaemic diabetic ketoacidosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Failure to thrive

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Fluid overload

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Fluid retention

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Gout

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Hypercalcaemia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Hyperglycaemia

0.43%

37/8574 • Number of events 49 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.64%

55/8569 • Number of events 56 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Hyperglycaemic hyperosmolar nonketotic syndrome

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Hyperkalaemia

0.07%

6/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Hyperlipidaemia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Hypernatraemia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Hypertriglyceridaemia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Hyperuricaemia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Hypocalcaemia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Hypoglycaemia

0.80%

69/8574 • Number of events 86 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

1.0%

86/8569 • Number of events 101 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Hypokalaemia

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Hypomagnesaemia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Hyponatraemia

0.10%

9/8574 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Hypovolaemia

0.16%

14/8574 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Ketoacidosis

0.08%

7/8574 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Ketosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Lactic acidosis

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Latent autoimmune diabetes in adults

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Lipomatosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Malnutrition

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Metabolic acidosis

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Obesity

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Type 1 diabetes mellitus

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Type 2 diabetes mellitus

0.08%

7/8574 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Metabolism and nutrition disorders

Vitamin d deficiency

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Arthralgia

0.08%

7/8574 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Arthritis

0.16%

14/8574 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Arthritis reactive

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Arthropathy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Articular calcification

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Back pain

0.06%

5/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Bursitis

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Cervical spinal stenosis

0.07%

6/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Chondromalacia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Chondropathy

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Compartment syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Costochondritis

0.03%

3/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Diastasis recti abdominis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Dupuytren's contracture

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Extraskeletal ossification

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Facet joint syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Fasciitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Flank pain

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Foot deformity

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Fracture malunion

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Fracture nonunion

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Gouty arthritis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Haemarthrosis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Immunoglobulin g4 related disease

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Intervertebral disc compression

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Intervertebral disc degeneration

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Intervertebral disc disorder

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Intervertebral disc displacement

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Intervertebral disc protrusion

0.28%

24/8574 • Number of events 25 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.20%

17/8569 • Number of events 18 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Jaw cyst

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Joint ankylosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Joint contracture

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Ligament calcification

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Lumbar spinal stenosis

0.16%

14/8574 • Number of events 15 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.21%

18/8569 • Number of events 18 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Meniscal degeneration

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Mobility decreased

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Muscle fibrosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Muscle haemorrhage

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Muscle spasms

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Muscular weakness

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain

0.14%

12/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.28%

24/8569 • Number of events 25 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Musculoskeletal pain

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Myalgia

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Myositis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Neck pain

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Neuropathic arthropathy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Osteitis

0.03%

3/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Osteoarthritis

1.2%

103/8574 • Number of events 114 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

1.1%

92/8569 • Number of events 102 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Osteochondrosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Osteolysis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Osteonecrosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Osteoporosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Osteoporotic fracture

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Pain in extremity

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Pain in jaw

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Patellofemoral pain syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Pathological fracture

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Periarthritis

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Polyarthritis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Polymyalgia rheumatica

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Pseudarthrosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Psoriatic arthropathy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Rhabdomyolysis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Rheumatoid arthritis

0.08%

7/8574 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Rotator cuff syndrome

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.19%

16/8569 • Number of events 16 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Sjogren's syndrome

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Spinal column stenosis

0.13%

11/8574 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.14%

12/8569 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Spinal ligament ossification

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Spinal osteoarthritis

0.10%

9/8574 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Spinal pain

0.05%

4/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Spondylitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Spondylolisthesis

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Synovial cyst

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Tendonitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Tenosynovitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Tenosynovitis stenosans

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Trigger finger

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Vertebral foraminal stenosis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Musculoskeletal and connective tissue disorders

Vertebral lesion

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Acral lentiginous melanoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Acute myeloid leukaemia

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Acute myelomonocytic leukaemia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma gastric

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma of appendix

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma of colon

0.23%

20/8574 • Number of events 20 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.21%

18/8569 • Number of events 18 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma pancreas

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenoid cystic carcinoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenoma benign

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adrenal adenoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adrenal neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adrenocortical carcinoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Anal squamous cell carcinoma

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Anaplastic astrocytoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Anaplastic large-cell lymphoma

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

B-cell lymphoma

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Basal cell carcinoma

0.40%

34/8574 • Number of events 42 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.32%

27/8569 • Number of events 37 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Basosquamous carcinoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign breast neoplasm

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign ear neoplasm

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign gastric neoplasm

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign gastrointestinal neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign hepatic neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign laryngeal neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign lung neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign lymph node neoplasm

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign neoplasm of adrenal gland

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign neoplasm of bladder

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign neoplasm of spinal cord

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign neoplasm of thyroid gland

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign ovarian tumour

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign pancreatic neoplasm

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign renal neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign salivary gland neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign soft tissue neoplasm

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder cancer

0.14%

12/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.29%

25/8569 • Number of events 25 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder cancer recurrent

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder cancer stage 0, with cancer in situ

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder cancer stage ii

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder neoplasm

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder papilloma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder transitional cell carcinoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder transitional cell carcinoma metastatic

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bone cancer

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bone cancer metastatic

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bone neoplasm

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bowen's disease

0.02%

2/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Brain neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Brain neoplasm benign

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Brain neoplasm malignant

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast cancer

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast cancer female

0.22%

19/8574 • Number of events 20 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.23%

20/8569 • Number of events 22 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast cancer metastatic

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bronchial carcinoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Cancer pain

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Carcinoid tumour of the duodenum

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Carcinoid tumour of the small bowel

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Central nervous system lymphoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Cervix carcinoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Cholangiocarcinoma

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Chondromatosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Chondrosarcoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Chronic leukaemia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Chronic lymphocytic leukaemia

0.08%

7/8574 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Chronic myeloid leukaemia

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Clear cell renal cell carcinoma

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon adenoma

0.09%

8/8574 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon cancer

0.19%

16/8574 • Number of events 17 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.19%

16/8569 • Number of events 16 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon cancer metastatic

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon neoplasm

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colorectal adenocarcinoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colorectal cancer

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colorectal cancer metastatic

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Dermatofibrosarcoma protuberans

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Diffuse large b-cell lymphoma

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Diffuse large b-cell lymphoma stage i

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Ductal adenocarcinoma of pancreas

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Endometrial adenocarcinoma

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Endometrial cancer

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Endometrial cancer metastatic

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Endometrial cancer stage i

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Fallopian tube cancer metastatic

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Fibroadenoma of breast

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Follicular thyroid cancer

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gallbladder adenocarcinoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gallbladder cancer metastatic

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gallbladder neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastric adenoma

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastric cancer

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastric cancer stage 0

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastric cancer stage iii

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastrointestinal adenocarcinoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastrointestinal carcinoma

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastrointestinal stromal cancer

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastrointestinal stromal tumour

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastrointestinal tract adenoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gingival cancer

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Glioblastoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Glioblastoma multiforme

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Glottis carcinoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Haemangioma

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Haemangiopericytoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Hairy cell leukaemia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Hepatic cancer

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Hepatic cancer metastatic

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Hepatocellular carcinoma

0.09%

8/8574 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Hodgkin's disease

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Hypopharyngeal cancer

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Infected neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intestinal adenocarcinoma

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intraductal proliferative breast lesion

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Invasive breast carcinoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Invasive ductal breast carcinoma

0.10%

9/8574 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Invasive lobular breast carcinoma

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Juvenile melanoma benign

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Keratoacanthoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Large intestine benign neoplasm

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Laryngeal cancer

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Laryngeal cancer metastatic

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Laryngeal squamous cell carcinoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lentigo maligna

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Leukaemia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lipoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Liposarcoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung adenocarcinoma

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung adenocarcinoma stage iii

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung cancer metastatic

0.13%

11/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.16%

14/8569 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung carcinoma cell type unspecified stage 0

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung carcinoma cell type unspecified stage iv

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung neoplasm

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung neoplasm malignant

0.14%

12/8574 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.25%

21/8569 • Number of events 21 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung squamous cell carcinoma metastatic

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lymphocytic leukaemia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lymphoma

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant anorectal neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant melanoma

0.15%

13/8574 • Number of events 17 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.14%

12/8569 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant melanoma in situ

0.07%

6/8574 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant neoplasm of ampulla of vater

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant neoplasm of pleura metastatic

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant neoplasm of renal pelvis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant neoplasm of unknown primary site

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant peritoneal neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant pleural effusion

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Melanocytic naevus

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Melanoma recurrent

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Meningioma

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Meningioma benign

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Mesothelioma malignant

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to adrenals

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to bone

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to central nervous system

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to lung

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to lymph nodes

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to peritoneum

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to rectum

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to spinal cord

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to spine

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastatic bronchial carcinoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastatic carcinoma of the bladder

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastatic gastric cancer

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastatic malignant melanoma

0.03%

3/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastatic neoplasm

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastatic renal cell carcinoma

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastatic squamous cell carcinoma

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Monoclonal gammopathy

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Myelodysplastic syndrome

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Myeloproliferative neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Nasopharyngeal cancer

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Neoplasm malignant

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Neoplasm prostate

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Neoplasm skin

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Neuroendocrine tumour

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Neuroendocrine tumour of the lung

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Neuroendocrine tumour of the lung metastatic

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-hodgkin's lymphoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-hodgkin's lymphoma stage iv

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-small cell lung cancer

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-small cell lung cancer metastatic

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-small cell lung cancer recurrent

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-small cell lung cancer stage iv

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Ocular neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Oesophageal adenocarcinoma

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Oesophageal carcinoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Oesophageal squamous cell carcinoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Oral neoplasm benign

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Oropharyngeal cancer

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Osteoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Ovarian adenoma

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Ovarian cancer

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Ovarian cancer metastatic

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Ovarian epithelial cancer

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Ovarian neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pancreatic carcinoma

0.10%

9/8574 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pancreatic carcinoma metastatic

0.09%

8/8574 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pancreatic neoplasm

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pancreatic neuroendocrine tumour

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pancreatoblastoma

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Papillary cystadenoma lymphomatosum

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Papillary renal cell carcinoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Papillary serous endometrial carcinoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Papillary thyroid cancer

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Papillary tumour of renal pelvis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Parathyroid tumour benign

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pelvic neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Penile squamous cell carcinoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Peritoneal carcinoma metastatic

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Phaeochromocytoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pharyngeal cancer

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pituitary tumour

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pituitary tumour benign

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Plasma cell leukaemia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Plasma cell myeloma

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pleomorphic adenoma

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Prostate cancer

0.80%

69/8574 • Number of events 70 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.64%

55/8569 • Number of events 55 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Prostate cancer metastatic

0.07%

6/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Prostate cancer recurrent

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Prostate cancer stage iv

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Prostatic adenoma

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Rectal adenocarcinoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Rectal adenoma

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Rectal cancer

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Rectal cancer metastatic

0.02%

2/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Renal cancer

0.12%

10/8574 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Renal cell carcinoma

0.12%

10/8574 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Renal neoplasm

0.07%

6/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Retro-orbital neoplasm

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Salivary gland cancer

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Salivary gland neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Sebaceous carcinoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Seborrhoeic keratosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Signet-ring cell carcinoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Small cell lung cancer

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Small cell lung cancer extensive stage

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Small cell lung cancer metastatic

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Small intestine adenocarcinoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Soft tissue sarcoma

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Spinal cord neoplasm

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma

0.09%

8/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.12%

10/8569 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma of lung

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma of skin

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma of the oral cavity

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma of the tongue

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

T-cell lymphoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Throat cancer

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Thyroid adenoma

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Thyroid cancer

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Thyroid cancer metastatic

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Thyroid neoplasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Tongue neoplasm malignant stage unspecified

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Tonsil cancer

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Transitional cell cancer of the renal pelvis and ureter

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Transitional cell carcinoma

0.13%

11/8574 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.14%

12/8569 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Transitional cell carcinoma metastatic

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Transitional cell carcinoma recurrent

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Tumour obstruction

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Uterine cancer

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Uterine leiomyoma

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Vaginal cancer stage 0

0.01%

1/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Vocal cord neoplasm

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Vulval cancer

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Vulval cancer stage 0

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Amnesia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Amyotrophic lateral sclerosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Aphasia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Arachnoid cyst

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Ataxia

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Autonomic failure syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Balance disorder

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Basal ganglia infarction

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Basilar artery perforation

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Brain injury

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Brain oedema

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Brain stem haemorrhage

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Brain stem infarction

0.07%

6/8574 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Brain stem stroke

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Burning sensation

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Carotid arteriosclerosis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Carotid artery insufficiency

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Carotid artery occlusion

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Carotid artery stenosis

0.31%

27/8574 • Number of events 27 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.25%

21/8569 • Number of events 22 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Carotid sinus syndrome

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Carpal tunnel syndrome

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cerebellar ataxia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cerebellar haemorrhage

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cerebellar infarction

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cerebellar stroke

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cerebral artery embolism

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cerebral artery occlusion

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cerebral atrophy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cerebral haematoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cerebral haemorrhage

0.08%

7/8574 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cerebral infarction

0.28%

24/8574 • Number of events 27 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.37%

32/8569 • Number of events 33 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cerebral ischaemia

0.07%

6/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cerebrovascular accident

1.2%

102/8574 • Number of events 112 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

1.0%

88/8569 • Number of events 94 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cerebrovascular disorder

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cerebrovascular insufficiency

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cervical cord compression

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cervical radiculopathy

0.03%

3/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cervicobrachial syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cluster headache

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cognitive disorder

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Coma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Cranial nerve palsies multiple

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Dementia

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Dementia alzheimer's type

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Dementia with lewy bodies

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Demyelinating polyneuropathy

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Diabetic autonomic neuropathy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Diabetic coma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Diabetic hyperosmolar coma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Diabetic neuropathy

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Dizziness

0.16%

14/8574 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.11%

9/8569 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Dizziness postural

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Dysarthria

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Dystonic tremor

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Embolic stroke

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Encephalopathy

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Epilepsy

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Essential tremor

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Facial paralysis

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Facial paresis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Focal dyscognitive seizures

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Generalised tonic-clonic seizure

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Guillain-barre syndrome

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Haemorrhage intracranial

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Haemorrhagic cerebral infarction

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Haemorrhagic stroke

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.13%

11/8569 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Haemorrhagic transformation stroke

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Headache

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Hemianopia homonymous

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Hemiparesis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Hepatic encephalopathy

0.03%

3/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Hydrocephalus

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Hypertensive encephalopathy

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Hypoaesthesia

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Hypoglycaemic coma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Hypoglycaemic encephalopathy

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Hypoglycaemic unconsciousness

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Hypokinesia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Hypoxic-ischaemic encephalopathy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Iiird nerve paralysis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Intensive care unit acquired weakness

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Intracranial aneurysm

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Intraventricular haemorrhage

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Ischaemic cerebral infarction

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Ischaemic neuropathy

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Ischaemic stroke

1.1%

97/8574 • Number of events 105 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

1.1%

90/8569 • Number of events 99 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Lacunar infarction

0.09%

8/8574 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.16%

14/8569 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Lacunar stroke

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Lateral medullary syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Loss of consciousness

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Lumbar radiculopathy

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Lumbosacral radiculopathy

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Medication overuse headache

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Memory impairment

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Metabolic encephalopathy

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Migraine

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Multiple system atrophy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Muscle contractions involuntary

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Myasthenia gravis

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Myelopathy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Nerve compression

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Nervous system disorder

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Neuralgia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Neurodegenerative disorder

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Neurological symptom

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Neuropathy peripheral

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Normal pressure hydrocephalus

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Occipital neuralgia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Paraesthesia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Paraparesis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Parkinson's disease

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Partial seizures

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Peroneal nerve palsy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Polyneuropathy

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Post herpetic neuralgia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Postictal paralysis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Presyncope

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Quadriplegia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Radicular pain

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Radicular syndrome

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Radiculopathy

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Ruptured cerebral aneurysm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Sciatica

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Seizure

0.06%

5/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.12%

10/8569 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Simple partial seizures

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Somnolence

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Spinal claudication

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Spondylitic myelopathy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Status epilepticus

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Stiff person syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Stroke in evolution

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Subdural hygroma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Syncope

0.43%

37/8574 • Number of events 38 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.48%

41/8569 • Number of events 44 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Tension headache

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Thalamic infarction

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Thoracic outlet syndrome

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Thrombotic cerebral infarction

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Thrombotic stroke

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Toxic encephalopathy

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Toxic neuropathy

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Transient ischaemic attack

0.79%

68/8574 • Number of events 76 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.63%

54/8569 • Number of events 59 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Tremor

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Vith nerve paralysis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Vith nerve paresis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Vascular dementia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Vascular encephalopathy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Vertebral artery stenosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Vertebrobasilar insufficiency

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Vertigo cns origin

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Vocal cord paralysis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Nervous system disorders

Wernicke-korsakoff syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Product Issues

Device breakage

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Product Issues

Device dislocation

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Product Issues

Device failure

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Product Issues

Device lead damage

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Product Issues

Device malfunction

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Product Issues

Device occlusion

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Product Issues

Stent malfunction

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Acute psychosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Adjustment disorder

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Agitation

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Alcohol withdrawal syndrome

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Anxiety

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Anxiety disorder

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Completed suicide

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Confusional state

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.14%

12/8569 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Conversion disorder

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Delirium

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Depressed mood

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Depression

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.15%

13/8569 • Number of events 15 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Drug abuse

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Hallucination

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Hypomania

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Major depression

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Mental status changes

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Mood disorder due to a general medical condition

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Panic attack

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Post-traumatic stress disorder

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Restlessness

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Schizoaffective disorder

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Schizoaffective disorder depressive type

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Schizophrenia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Sleep disorder

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Stress

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Suicidal ideation

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Psychiatric disorders

Suicide attempt

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Acute kidney injury

1.1%

94/8574 • Number of events 96 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

1.5%

127/8569 • Number of events 152 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Azotaemia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Bladder disorder

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Bladder mass

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Bladder outlet obstruction

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Bladder perforation

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Bladder prolapse

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Calculus bladder

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Calculus urethral

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Calculus urinary

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Chronic kidney disease

0.10%

9/8574 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.15%

13/8569 • Number of events 17 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Cystitis glandularis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Cystitis haemorrhagic

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Cystitis noninfective

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Cystitis ulcerative

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Diabetic nephropathy

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Dysuria

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

End stage renal disease

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Glomerulonephritis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Haematuria

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.19%

16/8569 • Number of events 19 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Hydronephrosis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Ketonuria

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Lower urinary tract symptoms

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Myeloma cast nephropathy

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Nephrolithiasis

0.16%

14/8574 • Number of events 16 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.21%

18/8569 • Number of events 18 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Nephrotic syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Oedematous kidney

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Pelvi-ureteric obstruction

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Pollakiuria

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Proteinuria

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Renal artery stenosis

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Renal colic

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Renal cyst

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Renal cyst ruptured

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Renal disorder

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Renal failure

0.12%

10/8574 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.20%

17/8569 • Number of events 17 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Renal haematoma

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Renal impairment

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.14%

12/8569 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Renal infarct

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Renal injury

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Renal tubular acidosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Renal tubular necrosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Stress urinary incontinence

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Ureteric stenosis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Ureterolithiasis

0.06%

5/8574 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.20%

17/8569 • Number of events 21 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Urethral meatus stenosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Urethral obstruction

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Urethral stenosis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Urinary bladder haemorrhage

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Urinary bladder polyp

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Urinary incontinence

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Urinary retention

0.09%

8/8574 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.12%

10/8569 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Renal and urinary disorders

Urinary tract obstruction

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Acquired hydrocele

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Acquired phimosis

0.13%

11/8574 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Balanoposthitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Benign prostatic hyperplasia

0.33%

28/8574 • Number of events 30 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.36%

31/8569 • Number of events 31 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Breast mass

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Breast pain

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Cervical dysplasia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Colpocele

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Cystocele

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Endometrial hyperplasia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Endometrial hypertrophy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Erectile dysfunction

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Female genital tract fistula

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Gynaecomastia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Hydrosalpinx

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Ovarian cyst

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Pelvic haemorrhage

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Pelvic prolapse

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Penile necrosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Peyronie's disease

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Postmenopausal haemorrhage

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Prostatic disorder

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Prostatitis

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 9 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Prostatomegaly

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Rectocele

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Testicular cyst

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Uterine polyp

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Uterine prolapse

0.07%

6/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Uterovaginal prolapse

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Vaginal dysplasia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Vaginal prolapse

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Reproductive system and breast disorders

Varicocele

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Acute pulmonary oedema

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.09%

8/8569 • Number of events 8 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Acute respiratory distress syndrome

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure

0.43%

37/8574 • Number of events 41 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.50%

43/8569 • Number of events 50 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Alveolitis allergic

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Apnoea

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Aspiration

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Asthma

0.07%

6/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.21%

18/8569 • Number of events 21 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Asthma-chronic obstructive pulmonary disease overlap syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Asthmatic crisis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Atelectasis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Bronchial hyperreactivity

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Bronchiectasis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Bronchitis chronic

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Bronchospasm

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease

0.63%

54/8574 • Number of events 81 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.63%

54/8569 • Number of events 90 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Chronic respiratory failure

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Dyspnoea

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.25%

21/8569 • Number of events 22 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Dyspnoea exertional

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Emphysema

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Epistaxis

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Haemoptysis

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Haemothorax

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Hydrothorax

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Hypoxia

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Idiopathic pulmonary fibrosis

0.02%

2/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Interstitial lung disease

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Lung disorder

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Lung infiltration

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Nasal polyps

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Nasal septum deviation

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Obstructive airways disorder

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Paraneoplastic pleural effusion

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pickwickian syndrome

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pleural effusion

0.07%

6/8574 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.15%

13/8569 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pleural thickening

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pleurisy

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pleuritic pain

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pneumonia aspiration

0.21%

18/8574 • Number of events 19 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.12%

10/8569 • Number of events 10 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pneumonitis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pneumothorax

0.07%

6/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pulmonary amyloidosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pulmonary arterial hypertension

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pulmonary congestion

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism

0.30%

26/8574 • Number of events 26 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.32%

27/8569 • Number of events 27 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pulmonary fibrosis

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pulmonary haemorrhage

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pulmonary hypertension

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 19 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pulmonary infarction

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pulmonary mass

0.02%

2/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.13%

11/8569 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pulmonary oedema

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.18%

15/8569 • Number of events 16 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Pulmonary thrombosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Reflux laryngitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Respiratory acidosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Respiratory arrest

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Respiratory distress

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Respiratory failure

0.34%

29/8574 • Number of events 30 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.28%

24/8569 • Number of events 28 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Restrictive pulmonary disease

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Rheumatoid lung

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Rhinitis hypertrophic

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Sleep apnoea syndrome

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Respiratory, thoracic and mediastinal disorders

Vocal cord leukoplakia

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Actinic keratosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Angioedema

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Decubitus ulcer

0.02%

2/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Dermal cyst

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Dermatitis contact

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Diabetic bullosis

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Diabetic foot

0.43%

37/8574 • Number of events 45 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.34%

29/8569 • Number of events 34 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Diabetic ulcer

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Eczema

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Erythema multiforme

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Fixed eruption

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Henoch-schonlein purpura

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Hidradenitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Hypersensitivity vasculitis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Ischaemic skin ulcer

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Keloid scar

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Lichen planus

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Lichen sclerosus

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Melanocytic hyperplasia

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Neuropathic ulcer

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Purpura

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Pyoderma gangrenosum

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Skin swelling

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Skin ulcer

0.28%

24/8574 • Number of events 28 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.27%

23/8569 • Number of events 26 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Stasis dermatitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Toxic skin eruption

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Skin and subcutaneous tissue disorders

Urticaria

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Surgical and medical procedures

Hospitalisation

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Accelerated hypertension

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Angiopathy

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Aortic aneurysm

0.14%

12/8574 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.12%

10/8569 • Number of events 11 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Aortic aneurysm rupture

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Aortic dilatation

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Aortic dissection

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Aortic stenosis

0.26%

22/8574 • Number of events 22 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.20%

17/8569 • Number of events 17 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Arterial disorder

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Arterial insufficiency

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Arterial occlusive disease

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Arterial perforation

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Arterial thrombosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Arteriosclerosis

0.05%

4/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Arteriovenous fistula

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Arteritis

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Bleeding varicose vein

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Blood pressure fluctuation

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Circulatory collapse

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Claudication of jaw muscles

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Deep vein thrombosis

0.20%

17/8574 • Number of events 18 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.14%

12/8569 • Number of events 12 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Diabetic vascular disorder

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Dry gangrene

0.03%

3/8574 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Embolism

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Essential hypertension

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Extremity necrosis

0.08%

7/8574 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Femoral artery aneurysm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Femoral artery embolism

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Haematoma

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.07%

6/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Haemorrhagic vasculitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Hypertension

0.31%

27/8574 • Number of events 28 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.32%

27/8569 • Number of events 31 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Hypertensive crisis

0.16%

14/8574 • Number of events 21 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.28%

24/8569 • Number of events 28 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Hypertensive emergency

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.08%

7/8569 • Number of events 7 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Hypotension

0.33%

28/8574 • Number of events 29 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.16%

14/8569 • Number of events 14 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Hypovolaemic shock

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Iliac artery disease

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Iliac artery embolism

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Iliac artery occlusion

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Intermittent claudication

0.06%

5/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.04%

3/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Internal haemorrhage

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Ischaemia

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Ischaemic limb pain

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Jugular vein thrombosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Leriche syndrome

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Lymphatic fistula

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Lymphoedema

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Malignant hypertension

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Microangiopathy

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Orthostatic hypotension

0.07%

6/8574 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.14%

12/8569 • Number of events 13 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Peripheral arterial occlusive disease

0.50%

43/8574 • Number of events 56 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.57%

49/8569 • Number of events 53 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Peripheral artery aneurysm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Peripheral artery dissection

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Peripheral artery haematoma

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Peripheral artery occlusion

0.16%

14/8574 • Number of events 18 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.18%

15/8569 • Number of events 20 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Peripheral artery stenosis

0.27%

23/8574 • Number of events 36 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.23%

20/8569 • Number of events 22 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Peripheral artery thrombosis

0.05%

4/8574 • Number of events 5 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.05%

4/8569 • Number of events 4 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Peripheral embolism

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Peripheral ischaemia

0.35%

30/8574 • Number of events 32 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.41%

35/8569 • Number of events 41 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Peripheral vascular disorder

0.40%

34/8574 • Number of events 46 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.22%

19/8569 • Number of events 21 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Peripheral venous disease

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Phlebitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Raynaud's phenomenon

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Shock

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Shock haemorrhagic

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Subclavian artery occlusion

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Subclavian artery stenosis

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Subclavian steal syndrome

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Superior vena cava stenosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Temporal arteritis

0.01%

1/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.02%

2/8569 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Thromboangiitis obliterans

0.00%

0/8574 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Thrombophlebitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Thrombophlebitis superficial

0.02%

2/8574 • Number of events 2 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Thrombosis

0.03%

3/8574 • Number of events 3 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.01%

1/8569 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Varicose ulceration

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Varicose vein

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.06%

5/8569 • Number of events 6 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Vascular occlusion

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Vasculitis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Vasospasm

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Venous thrombosis

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Vascular disorders

Venous thrombosis limb

0.01%

1/8574 • Number of events 1 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

0.00%

0/8569 • up to 5.2 years

All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.

Trial Outcomes & Findings for Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events (NCT NCT01730534)

Results Overview

Participant Flow

Participant milestones

Reasons for withdrawal

Baseline Characteristics

Baseline characteristics by cohort

PRIMARY outcome

Outcome measures

PRIMARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

Adverse Events

Dapa 10 mg

Placebo

Serious adverse events

Other adverse events

Additional Information

Global Study Leader

Results disclosure agreements

Measure	Dapa 10 mg n=8574 participants at risk Description (Arm-group)	Placebo n=8569 participants at risk Description (Arm-group)
Renal and urinary disorders Acute kidney injury	0.96% 82/8574 • Number of events 91 • up to 5.2 years All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.	1.3% 112/8569 • Number of events 129 • up to 5.2 years All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.
Renal and urinary disorders Chronic kidney disease	0.90% 77/8574 • Number of events 78 • up to 5.2 years All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.	1.2% 104/8569 • Number of events 108 • up to 5.2 years All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.
Renal and urinary disorders Renal impairment	1.4% 121/8574 • Number of events 126 • up to 5.2 years All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.	1.7% 146/8569 • Number of events 159 • up to 5.2 years All-Cause Mortality was assessed for all participants. Serious and Other Adverse Events were only assessed for the Safety Analysis Population, which included participants that received at least one dose of study drug and who have data observed at any time after first randomized dose until the end of the study.