Trial Outcomes & Findings for Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease (NCT NCT02540993)

Participant milestones
Measure	Finerenone Participants received finerenone 10 mg or 20 mg once daily in addition to standard of care therapy	Placebo Participants received matching placebo once daily in addition to standard of care therapy
Overall Study STARTED	2866	2868
Overall Study Included in FAS	2833	2841
Overall Study Treated	2827	2831
Overall Study COMPLETED	2824	2832
Overall Study NOT COMPLETED	42	36

Reasons for withdrawal
Measure	Finerenone Participants received finerenone 10 mg or 20 mg once daily in addition to standard of care therapy	Placebo Participants received matching placebo once daily in addition to standard of care therapy
Overall Study Lost to Follow-up	5	3
Overall Study Withdrawal by Subject	4	6
Overall Study GCP violations	33	27

Baseline characteristics by cohort
Measure	Finerenone n=2833 Participants Participants received finerenone 10 mg or 20 mg once daily in addition to standard of care therapy	Placebo n=2841 Participants Participants received matching placebo once daily in addition to standard of care therapy	Total n=5674 Participants Total of all reporting groups
Age, Continuous	65.44 Years STANDARD_DEVIATION 8.94 • n=2833 Participants	65.67 Years STANDARD_DEVIATION 9.16 • n=2841 Participants	65.56 Years STANDARD_DEVIATION 9.05 • n=5674 Participants
Sex: Female, Male Female	880 Participants n=2833 Participants	811 Participants n=2841 Participants	1691 Participants n=5674 Participants
Sex: Female, Male Male	1953 Participants n=2833 Participants	2030 Participants n=2841 Participants	3983 Participants n=5674 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	447 Participants n=2833 Participants	431 Participants n=2841 Participants	878 Participants n=5674 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2376 Participants n=2833 Participants	2397 Participants n=2841 Participants	4773 Participants n=5674 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	10 Participants n=2833 Participants	13 Participants n=2841 Participants	23 Participants n=5674 Participants
Race (NIH/OMB) American Indian or Alaska Native	78 Participants n=2833 Participants	76 Participants n=2841 Participants	154 Participants n=5674 Participants
Race (NIH/OMB) Asian	717 Participants n=2833 Participants	723 Participants n=2841 Participants	1440 Participants n=5674 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	11 Participants n=2833 Participants	7 Participants n=2841 Participants	18 Participants n=5674 Participants
Race (NIH/OMB) Black or African American	140 Participants n=2833 Participants	124 Participants n=2841 Participants	264 Participants n=5674 Participants
Race (NIH/OMB) White	1777 Participants n=2833 Participants	1815 Participants n=2841 Participants	3592 Participants n=5674 Participants
Race (NIH/OMB) More than one race	101 Participants n=2833 Participants	86 Participants n=2841 Participants	187 Participants n=5674 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=2833 Participants	10 Participants n=2841 Participants	19 Participants n=5674 Participants
Urinary albumin-to-creatinine ratio (UACR)	832.72 milligram/gram (mg/g) n=2831 Participants • Participants in FAS with evaluable data	867.01 milligram/gram (mg/g) n=2840 Participants • Participants in FAS with evaluable data	851.87 milligram/gram (mg/g) n=5671 Participants • Participants in FAS with evaluable data
Estimated glomerular filtration rate (eGFR)	44.36 mL/min/1.73m^2 STANDARD_DEVIATION 12.54 • n=2832 Participants • Participants in FAS with evaluable data	44.32 mL/min/1.73m^2 STANDARD_DEVIATION 12.57 • n=2840 Participants • Participants in FAS with evaluable data	44.34 mL/min/1.73m^2 STANDARD_DEVIATION 12.56 • n=5672 Participants • Participants in FAS with evaluable data

Outcome measures
Measure	Finerenone n=2833 Participants Participants received finerenone 10 mg or 20 mg once daily in addition to standard of care therapy	Placebo n=2841 Participants Participants received matching placebo once daily in addition to standard of care therapy
The First Occurrence of the Composite Endpoint of Onset of Kidney Failure, a Sustained Decrease of eGFR ≥40% From Baseline Over at Least 4 Weeks, or Renal Death	504 Participants	600 Participants

Outcome measures
Measure	Finerenone n=2833 Participants Participants received finerenone 10 mg or 20 mg once daily in addition to standard of care therapy	Placebo n=2841 Participants Participants received matching placebo once daily in addition to standard of care therapy
The First Occurrence of the Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke, or Hospitalization for Heart Failure	367 Participants	420 Participants

Outcome measures
Measure	Finerenone n=2833 Participants Participants received finerenone 10 mg or 20 mg once daily in addition to standard of care therapy	Placebo n=2841 Participants Participants received matching placebo once daily in addition to standard of care therapy
All-cause Mortality	219 Participants	244 Participants

Outcome measures
Measure	Finerenone n=2833 Participants Participants received finerenone 10 mg or 20 mg once daily in addition to standard of care therapy	Placebo n=2841 Participants Participants received matching placebo once daily in addition to standard of care therapy
All-cause Hospitalization	1263 Participants	1321 Participants

Outcome measures
Measure	Finerenone n=2711 Participants Participants received finerenone 10 mg or 20 mg once daily in addition to standard of care therapy	Placebo n=2705 Participants Participants received matching placebo once daily in addition to standard of care therapy
Change in Urinary Albumin-to-creatinine Ratio (UACR) From Baseline to Month 4	0.655 Ratio Interval 0.637 to 0.673	0.952 Ratio Interval 0.927 to 0.979

Outcome measures
Measure	Finerenone n=2833 Participants Participants received finerenone 10 mg or 20 mg once daily in addition to standard of care therapy	Placebo n=2841 Participants Participants received matching placebo once daily in addition to standard of care therapy
The First Occurrence of the Composite Endpoint of Onset of Kidney Failure, a Sustained Decrease in eGFR of ≥57% From Baseline Over at Least 4 Weeks, or Renal Death	252 Participants	326 Participants

Blood and lymphatic system disorders

Anaemia

0.50%

14/2827 • Number of events 14 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.67%

19/2831 • Number of events 21 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Blood and lymphatic system disorders

Febrile neutropenia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Blood and lymphatic system disorders

Iron deficiency anaemia

0.18%

5/2827 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.21%

6/2831 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Blood and lymphatic system disorders

Lymphadenopathy

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Blood and lymphatic system disorders

Lymphadenopathy mediastinal

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Blood and lymphatic system disorders

Microcytic anaemia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Blood and lymphatic system disorders

Neutropenia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Blood and lymphatic system disorders

Normocytic anaemia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Blood and lymphatic system disorders

Pancytopenia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Blood and lymphatic system disorders

Thrombocytopenia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Blood and lymphatic system disorders

Nephrogenic anaemia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Blood and lymphatic system disorders

Blood loss anaemia

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Blood and lymphatic system disorders

Immune thrombocytopenia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Angina pectoris

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Angina unstable

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Aortic valve disease mixed

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Aortic valve stenosis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Arrhythmia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Arteriosclerosis coronary artery

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Atrial fibrillation

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Atrial flutter

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Atrioventricular block

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Bradycardia

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Cardiac arrest

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Cardiac asthma

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Cardiac failure

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.35%

10/2831 • Number of events 10 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Cardiac failure acute

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Cardiac failure chronic

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Cardiac failure congestive

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.28%

8/2831 • Number of events 8 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Cardio-respiratory arrest

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Cardiogenic shock

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Cardiomyopathy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Coronary artery disease

0.28%

8/2827 • Number of events 8 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Hypertensive heart disease

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Left ventricular failure

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Myocardial ischaemia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Atrial thrombosis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Left ventricular dysfunction

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Aortic valve calcification

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Acute coronary syndrome

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Bifascicular block

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Mitral valve disease

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Acute left ventricular failure

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Stress cardiomyopathy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Cardiorenal syndrome

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Sinus node dysfunction

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Cardiac disorders

Ischaemic mitral regurgitation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Congenital, familial and genetic disorders

Dermoid cyst

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Congenital, familial and genetic disorders

Factor VIII deficiency

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Congenital, familial and genetic disorders

Phimosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Congenital, familial and genetic disorders

Truncus arteriosus persistent

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Ear and labyrinth disorders

Deafness neurosensory

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Ear and labyrinth disorders

Ear pain

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Ear and labyrinth disorders

Tinnitus

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Ear and labyrinth disorders

Tympanic membrane perforation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Ear and labyrinth disorders

Vertigo

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Ear and labyrinth disorders

Vertigo positional

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Ear and labyrinth disorders

Vestibular disorder

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Ear and labyrinth disorders

Deafness unilateral

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Ear and labyrinth disorders

Sudden hearing loss

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Endocrine disorders

Goitre

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Endocrine disorders

Hyperthyroidism

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Endocrine disorders

Pituitary-dependent Cushing's syndrome

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Endocrine disorders

Thyroiditis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Endocrine disorders

Thyroid mass

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Blindness

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Cataract

0.67%

19/2827 • Number of events 22 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.42%

12/2831 • Number of events 15 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Cataract diabetic

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Cataract subcapsular

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Diabetic retinal oedema

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Diabetic retinopathy

0.11%

3/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.25%

7/2831 • Number of events 8 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Ectropion

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Eye disorder

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Eye haemorrhage

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Glaucoma

0.21%

6/2827 • Number of events 10 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Lens dislocation

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Macular oedema

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Open angle glaucoma

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Optic disc haemorrhage

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Papilloedema

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Pterygium

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Retinal artery occlusion

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Retinal detachment

0.14%

4/2827 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Retinal haemorrhage

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Retinopathy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Visual impairment

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Vitreous haemorrhage

0.21%

6/2827 • Number of events 8 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.25%

7/2831 • Number of events 9 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Macular hole

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Ulcerative keratitis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Rhegmatogenous retinal detachment

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Macular fibrosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Eye disorders

Tractional retinal detachment

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Abdominal pain

0.21%

6/2827 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Abdominal pain upper

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Anal fistula

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Ascites

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Change of bowel habit

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Chronic gastritis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Colitis

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Colitis ischaemic

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Constipation

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Dental caries

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Diarrhoea

0.25%

7/2827 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.21%

6/2831 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Diarrhoea haemorrhagic

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Diverticulum

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Diverticulum intestinal

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Diverticulum intestinal haemorrhagic

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Duodenal polyp

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Duodenal ulcer

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Duodenal ulcer haemorrhage

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Duodenal ulcer perforation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Duodenitis haemorrhagic

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Dyspepsia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Enterocolitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Gastric haemorrhage

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Gastric polyps

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Gastric ulcer haemorrhage

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Gastric ulcer perforation

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Gastritis

0.07%

2/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Gastritis erosive

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Gastritis haemorrhagic

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Gastrooesophageal reflux disease

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Gastroduodenal ulcer

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Gastrointestinal disorder

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Gastrointestinal haemorrhage

0.46%

13/2827 • Number of events 16 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.25%

7/2831 • Number of events 9 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Gastrointestinal necrosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Haematemesis

0.07%

2/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Haematochezia

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Haemorrhoids

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Ileus

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Impaired gastric emptying

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Inguinal hernia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Intestinal angina

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Intestinal ischaemia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Intestinal obstruction

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Intestinal perforation

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Melaena

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Nausea

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Oesophageal achalasia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Oesophageal ulcer haemorrhage

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Oesophagitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Pancreatic cyst

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Pancreatitis

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Pancreatitis acute

0.25%

7/2827 • Number of events 8 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.28%

8/2831 • Number of events 8 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Pancreatitis chronic

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Peptic ulcer haemorrhage

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Proctitis

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Rectal haemorrhage

0.21%

6/2827 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Rectal polyp

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Salivary gland calculus

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Small intestinal obstruction

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Umbilical hernia

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Upper gastrointestinal haemorrhage

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Vomiting

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Subileus

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Lower gastrointestinal haemorrhage

0.21%

6/2827 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Large intestine polyp

0.18%

5/2827 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.25%

7/2831 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Chilaiditi's syndrome

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Oedematous pancreatitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Small intestinal haemorrhage

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Abdominal strangulated hernia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Haemorrhoidal haemorrhage

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Varices oesophageal

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Faecaloma

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Gastrointestinal ulcer haemorrhage

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Alcoholic pancreatitis

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Retroperitoneal haematoma

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Abdominal hernia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Gastric mucosal lesion

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Gastrointestinal motility disorder

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Incarcerated umbilical hernia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Pancreatic duct stenosis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Haemorrhagic erosive gastritis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Functional gastrointestinal disorder

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Retroperitoneal mass

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Strangulated umbilical hernia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Intra-abdominal fluid collection

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Obstructive pancreatitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Gastrointestinal disorders

Gastrointestinal vascular malformation haemorrhagic

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Asthenia

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Chest discomfort

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Chest pain

0.46%

13/2827 • Number of events 15 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.64%

18/2831 • Number of events 20 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Death

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Fatigue

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Gait disturbance

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Generalised oedema

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Hypothermia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Malaise

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Mass

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Oedema

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Oedema peripheral

0.28%

8/2827 • Number of events 10 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.25%

7/2831 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Pyrexia

0.14%

4/2827 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Soft tissue inflammation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Swelling face

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Peripheral swelling

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Hernia pain

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

General physical health deterioration

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Oedema due to renal disease

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Inflammation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Non-cardiac chest pain

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Device intolerance

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Vascular stent stenosis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

General disorders

Multiple organ dysfunction syndrome

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Bile duct stone

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Biliary colic

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Cholangitis

0.07%

2/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Cholangitis acute

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Cholecystitis

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Cholecystitis acute

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.32%

9/2831 • Number of events 10 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Cholecystitis chronic

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Cholelithiasis

0.42%

12/2827 • Number of events 14 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Cholestasis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Hepatic cirrhosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Hepatic function abnormal

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Hepatitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Hepatitis acute

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Hepatitis alcoholic

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Jaundice cholestatic

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Liver disorder

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Bile duct obstruction

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Biliary dilatation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Hepatic lesion

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Hepatobiliary disorders

Drug-induced liver injury

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Immune system disorders

Drug hypersensitivity

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Abdominal wall abscess

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Appendicitis

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Appendicitis perforated

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Atypical pneumonia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Bacteraemia

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Bronchitis

0.32%

9/2827 • Number of events 9 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.46%

13/2831 • Number of events 15 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Campylobacter gastroenteritis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Carbuncle

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Cellulitis

0.92%

26/2827 • Number of events 30 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.78%

22/2831 • Number of events 23 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Chronic sinusitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Clostridium difficile colitis

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Cystitis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Dengue fever

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Diabetic gangrene

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Diverticulitis

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Ear infection

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Endocarditis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Endophthalmitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Epididymitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Epiglottitis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Erysipelas

0.39%

11/2827 • Number of events 11 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.49%

14/2831 • Number of events 16 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Fournier's gangrene

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Gangrene

0.18%

5/2827 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Gastroenteritis

0.32%

9/2827 • Number of events 9 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.46%

13/2831 • Number of events 13 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Gastroenteritis salmonella

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Gastroenteritis viral

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Hepatitis B

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Hepatitis viral

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Herpes zoster

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Infected skin ulcer

0.14%

4/2827 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Infection

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Influenza

0.25%

7/2827 • Number of events 8 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Kidney infection

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Labyrinthitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Leptospirosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Liver abscess

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Localised infection

0.25%

7/2827 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Lower respiratory tract infection

0.18%

5/2827 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Mastoiditis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Oesophageal candidiasis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Orchitis

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Osteomyelitis

0.50%

14/2827 • Number of events 14 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.42%

12/2831 • Number of events 12 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Osteomyelitis chronic

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Otitis externa

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Otitis media

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Paronychia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Periodontitis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Peritonitis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Pharyngitis streptococcal

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Pneumonia

2.5%

70/2827 • Number of events 75 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

3.6%

103/2831 • Number of events 115 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Pneumonia respiratory syncytial viral

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Pneumonia streptococcal

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Postoperative wound infection

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Prostatic abscess

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Pulmonary tuberculosis

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Pyelonephritis

0.25%

7/2827 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Pyelonephritis acute

0.18%

5/2827 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Pyelonephritis chronic

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Pyonephrosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Renal abscess

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Sepsis

0.53%

15/2827 • Number of events 15 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.60%

17/2831 • Number of events 18 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Septic shock

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Sinusitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Splenic abscess

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Subcutaneous abscess

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Tracheobronchitis

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Upper respiratory tract infection

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Urethritis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Urinary tract infection

0.74%

21/2827 • Number of events 22 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.81%

23/2831 • Number of events 30 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Viral infection

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Viral pericarditis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Viral tracheitis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Wound infection

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Oral infection

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Urosepsis

0.18%

5/2827 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.25%

7/2831 • Number of events 9 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Anal abscess

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Rectal abscess

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Streptococcal sepsis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Pyelocystitis

0.07%

2/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Neutropenic sepsis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Peritonsillitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Groin abscess

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Abscess limb

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Burn infection

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Haematoma infection

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Chest wall abscess

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Pulmonary sepsis

0.18%

5/2827 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Febrile infection

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Escherichia urinary tract infection

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Arthritis bacterial

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Peritoneal tuberculosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Enterococcal sepsis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Clostridium difficile infection

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Staphylococcal sepsis

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Enteritis infectious

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Klebsiella bacteraemia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Viraemia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Acute hepatitis B

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Intervertebral discitis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Diabetic foot infection

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Abdominal abscess

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Pneumonia bacterial

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Borrelia infection

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Respiratory syncytial virus infection

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Herpes ophthalmic

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Peritonitis bacterial

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Soft tissue infection

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Urinary tract infection staphylococcal

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Respiratory tract infection

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Infective spondylitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Stoma site infection

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Dermo-hypodermitis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Post procedural sepsis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Post procedural infection

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

H1N1 influenza

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Device related sepsis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Infective exacerbation of bronchiectasis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Infected seroma

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Medical device site joint infection

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Infected bite

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Large intestine infection

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Nephritis bacterial

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Infections and infestations

Bullous erysipelas

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Accident

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Accidental overdose

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Acetabulum fracture

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Alcohol poisoning

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Ankle fracture

0.25%

7/2827 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Back injury

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Burns second degree

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Clavicle fracture

0.07%

2/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Concussion

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Dislocation of vertebra

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Facial bones fracture

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Fall

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.21%

6/2831 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Femoral neck fracture

0.25%

7/2827 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Femur fracture

0.21%

6/2827 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.32%

9/2831 • Number of events 9 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Fibula fracture

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Foot fracture

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Forearm fracture

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Hand fracture

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Head injury

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Heat stroke

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Hip fracture

0.21%

6/2827 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Humerus fracture

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.25%

7/2831 • Number of events 8 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Incisional hernia

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Injury

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Intentional overdose

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Joint dislocation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Muscle rupture

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Overdose

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Patella fracture

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Poisoning deliberate

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Radiation proctitis

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Radius fracture

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Rib fracture

0.18%

5/2827 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Road traffic accident

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Soft tissue injury

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Spinal cord injury cervical

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Spinal fracture

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Sternal fracture

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Subdural haematoma

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Subdural haemorrhage

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Tendon injury

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Tibia fracture

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Ulna fracture

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Wrist fracture

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Traumatic fracture

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Cervical vertebral fracture

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Lumbar vertebral fracture

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Thoracic vertebral fracture

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Muscle strain

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Contusion

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Post procedural haemorrhage

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Thermal burn

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Wound necrosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Inflammation of wound

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Arteriovenous fistula site complication

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Post concussion syndrome

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Skin laceration

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Incision site haematoma

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Joint injury

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Pelvic fracture

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Ligament injury

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Limb injury

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Skull fracture

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Chest injury

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Upper limb fracture

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Postoperative wound complication

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Lower limb fracture

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Shunt malfunction

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Post procedural inflammation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Abdominal wound dehiscence

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Toxicity to various agents

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Craniocerebral injury

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Meniscus injury

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Cardiac contusion

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Traumatic haemothorax

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Incarcerated incisional hernia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Vascular access malfunction

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Injury, poisoning and procedural complications

Ocular procedural complication

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Alanine aminotransferase increased

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Aspartate aminotransferase increased

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Biopsy kidney

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Blood creatine phosphokinase increased

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Blood creatine phosphokinase MB increased

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Blood creatinine increased

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Blood glucose increased

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Blood potassium increased

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Blood pressure increased

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Colonoscopy

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Endoscopy small intestine

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Gamma-glutamyltransferase increased

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Glomerular filtration rate decreased

0.18%

5/2827 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Heart rate increased

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Weight decreased

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Ejection fraction decreased

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Protein urine present

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Cardiac pacemaker evaluation

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Computerised tomogram abdomen

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Cardiac stress test abnormal

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Troponin T increased

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Blood alkaline phosphatase increased

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Light chain analysis increased

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Anticoagulation drug level above therapeutic

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Hepatic enzyme increased

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Arteriogram

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Inflammatory marker increased

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Influenza A virus test positive

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Cardiovascular examination

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Peripheral arteriogram

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Liver function test increased

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Investigations

Angiocardiogram

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Dehydration

0.25%

7/2827 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Diabetes mellitus

0.35%

10/2827 • Number of events 12 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.57%

16/2831 • Number of events 18 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Diabetes mellitus inadequate control

0.42%

12/2827 • Number of events 13 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.67%

19/2831 • Number of events 21 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Diabetic ketoacidosis

0.25%

7/2827 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.25%

7/2831 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Fluid overload

0.25%

7/2827 • Number of events 9 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.25%

7/2831 • Number of events 8 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Fluid retention

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Gout

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.25%

7/2831 • Number of events 8 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Hypercalcaemia

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Hyperglycaemia

0.60%

17/2827 • Number of events 20 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.81%

23/2831 • Number of events 26 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Hyperkalaemia

1.5%

42/2827 • Number of events 45 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.42%

12/2831 • Number of events 14 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Hyperosmolar state

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Hypervolaemia

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Hypocalcaemia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Hypoglycaemia

0.74%

21/2827 • Number of events 23 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

1.1%

31/2831 • Number of events 33 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Hypoglycaemia unawareness

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Hypokalaemia

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Hypomagnesaemia

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Hyponatraemia

0.28%

8/2827 • Number of events 12 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Hypoproteinaemia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Hypovolaemia

0.11%

3/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Ketoacidosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Metabolic acidosis

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Tumour lysis syndrome

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Calciphylaxis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Metabolic disorder

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Diabetic complication

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Malnutrition

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Decreased appetite

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Hyperglycaemic hyperosmolar nonketotic syndrome

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Type 2 diabetes mellitus

0.50%

14/2827 • Number of events 16 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.78%

22/2831 • Number of events 28 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Metabolism and nutrition disorders

Diabetic metabolic decompensation

0.42%

12/2827 • Number of events 15 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.49%

14/2831 • Number of events 15 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Arthralgia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Arthritis

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Back disorder

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Back pain

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Bursitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Cervical spinal stenosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Costochondritis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Flank pain

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Gouty arthritis

0.18%

5/2827 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Lumbar spinal stenosis

0.14%

4/2827 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.25%

7/2831 • Number of events 10 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Musculoskeletal pain

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Neck pain

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Neuropathic arthropathy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Osteitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Osteoarthritis

0.39%

11/2827 • Number of events 11 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.28%

8/2831 • Number of events 8 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Osteoarthropathy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Osteonecrosis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Pain in extremity

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Polymyalgia rheumatica

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Rhabdomyolysis

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Rheumatoid arthritis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Rotator cuff syndrome

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Spinal osteoarthritis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Tenosynovitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Musculoskeletal disorder

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Intervertebral disc protrusion

0.25%

7/2827 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.46%

13/2831 • Number of events 16 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Haematoma muscle

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Connective tissue inflammation

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Foot deformity

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Intervertebral disc degeneration

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Spondylitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Spondylolisthesis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Osteonecrosis of jaw

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Soft tissue necrosis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Spinal instability

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Limb mass

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Musculoskeletal and connective tissue disorders

Spinal stenosis

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Acute myeloid leukaemia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma gastric

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma of colon

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenoma benign

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adrenal adenoma

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

B-cell lymphoma stage IV

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Basal cell carcinoma

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign salivary gland neoplasm

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder cancer

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder cancer recurrent

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder neoplasm

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder squamous cell carcinoma stage unspecified

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder transitional cell carcinoma

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bowen's disease

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast cancer

0.14%

4/2827 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast neoplasm

0.04%

1/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Cholangiocarcinoma

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Chronic lymphocytic leukaemia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon cancer

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon cancer stage IV

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Diffuse large B-cell lymphoma recurrent

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Endometrial adenocarcinoma

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Fibroadenoma of breast

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Fibrosarcoma

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastric cancer

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastrointestinal carcinoma

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Haemangioma

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Hypergammaglobulinaemia benign monoclonal

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Laryngeal squamous cell carcinoma

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lentigo maligna

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lipoma

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung adenocarcinoma

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung carcinoma cell type unspecified stage IV

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung squamous cell carcinoma stage IV

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lymphoma

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant melanoma

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant neoplasm of ampulla of Vater

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to bone

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to liver

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to lung

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to lymph nodes

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to spine

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastatic malignant melanoma

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Myelodysplastic syndrome

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Nasal cavity cancer

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Neoplasm

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Neoplasm prostate

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Neuroendocrine carcinoma of the skin

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Oesophageal adenocarcinoma

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Oesophageal carcinoma

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Oropharyngeal cancer

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pancreatic carcinoma

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pancreatic carcinoma metastatic

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Penile cancer

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Plasma cell myeloma

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Prostate cancer metastatic

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Rectal adenocarcinoma

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Renal cancer

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Sarcoma

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Small cell lung cancer

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma of lung

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma of skin

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma of the oral cavity

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma of the tongue

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Superficial spreading melanoma stage unspecified

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Tongue neoplasm malignant stage unspecified

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Tonsil cancer

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Transitional cell carcinoma

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Vulval cancer stage 0

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon adenoma

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung cancer metastatic

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastatic renal cell carcinoma

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastrointestinal stromal tumour

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to spleen

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma pancreas

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Rectal cancer metastatic

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Oesophageal cancer metastatic

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast cancer metastatic

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Infected neoplasm

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Cancer pain

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gallbladder adenocarcinoma

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung neoplasm malignant

0.32%

9/2827 • Number of events 9 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to central nervous system

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pancreatic carcinoma stage IV

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Small cell lung cancer metastatic

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Prostate cancer

0.46%

13/2827 • Number of events 13 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Monoclonal gammopathy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign pancreatic neoplasm

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Brain neoplasm

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant urinary tract neoplasm

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colorectal cancer

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Renal neoplasm

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Salivary gland neoplasm

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pituitary tumour benign

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pancreatic neoplasm

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung neoplasm

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Tongue neoplasm

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Urethral neoplasm

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Renal cell carcinoma

0.07%

2/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Sarcoma metastatic

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Tumour rupture

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant neoplasm of unknown primary site

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Hepatocellular carcinoma

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Hepatobiliary cancer

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intraductal proliferative breast lesion

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Clear cell renal cell carcinoma

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Ductal adenocarcinoma of pancreas

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Angiomyofibroblastoma

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma metastatic

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Alcohol induced persisting dementia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Altered state of consciousness

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Aphasia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Brown-Sequard syndrome

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Carotid artery stenosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Carpal tunnel syndrome

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Cerebral haemorrhage

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Cerebral infarction

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Cerebral ischaemia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Cerebrovascular accident

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Cerebrovascular disorder

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Cervicobrachial syndrome

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Coma

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Cranial nerve palsies multiple

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Diabetic neuropathy

0.21%

6/2827 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Dizziness

0.21%

6/2827 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.35%

10/2831 • Number of events 10 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Drop attacks

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Dysarthria

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Epilepsy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Facial paralysis

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Headache

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Hemiparesis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Hepatic encephalopathy

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

IIIrd nerve paralysis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Lethargy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Loss of consciousness

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Migraine

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Myelopathy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Neuralgia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Neuropathy peripheral

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Polyneuropathy

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Post herpetic neuralgia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Presyncope

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Radiculopathy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Sciatica

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Seizure

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Subarachnoid haemorrhage

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Syncope

0.42%

12/2827 • Number of events 12 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.78%

22/2831 • Number of events 22 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Transient ischaemic attack

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Vertebrobasilar insufficiency

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Brain oedema

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Carotid artery occlusion

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Vertebral artery occlusion

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Arachnoid cyst

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Balance disorder

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Lacunar infarction

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Facial paresis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Neurodegenerative disorder

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Cerebral disorder

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Neuroglycopenia

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Cerebrovascular insufficiency

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Cerebral vasoconstriction

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Ischaemic cerebral infarction

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Ischaemic stroke

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Mononeuropathy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Vascular encephalopathy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Cerebral arteriosclerosis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Carotid arteriosclerosis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Thrombotic cerebral infarction

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Cerebral microangiopathy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Dementia with Lewy bodies

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Hypoxic-ischaemic encephalopathy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Secondary cerebellar degeneration

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Lumbosacral radiculopathy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Cerebral vascular occlusion

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Post stroke epilepsy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Hemianaesthesia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Nervous system disorders

Angiopathic neuropathy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Psychiatric disorders

Alcohol abuse

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Psychiatric disorders

Anxiety

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Psychiatric disorders

Confusional state

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Psychiatric disorders

Depression

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Psychiatric disorders

Insomnia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Psychiatric disorders

Mania

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Psychiatric disorders

Suicide attempt

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Psychiatric disorders

Mental status changes

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Psychiatric disorders

Bipolar disorder

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Psychiatric disorders

Major depression

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Azotaemia

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Calculus bladder

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Calculus urinary

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Chromaturia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Cystitis ulcerative

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Dysuria

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Glomerular vascular disorder

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Haematuria

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Hydronephrosis

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Intercapillary glomerulosclerosis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Nephrolithiasis

0.21%

6/2827 • Number of events 8 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Nephropathy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Nephropathy toxic

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Nephrosclerosis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Nephrotic syndrome

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.32%

9/2831 • Number of events 9 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Nocturia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Proteinuria

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Renal artery stenosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Renal colic

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Renal cyst

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Renal failure

0.25%

7/2827 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.25%

7/2831 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Renal haemorrhage

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Renal tubular acidosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Urinary incontinence

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Urinary retention

0.21%

6/2827 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Tubulointerstitial nephritis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Urinary bladder polyp

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Hypertensive nephropathy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Bladder cyst

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Urinary tract obstruction

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Diabetic nephropathy

0.64%

18/2827 • Number of events 23 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.57%

16/2831 • Number of events 19 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Renal mass

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Renal impairment

0.28%

8/2827 • Number of events 8 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.28%

8/2831 • Number of events 10 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Chronic kidney disease

0.42%

12/2827 • Number of events 12 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.78%

22/2831 • Number of events 26 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Urethral stenosis

0.07%

2/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Acute kidney injury

2.0%

56/2827 • Number of events 63 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

1.8%

51/2831 • Number of events 55 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Bladder outlet obstruction

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Perinephritis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

End stage renal disease

0.18%

5/2827 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Ureterolithiasis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Renal and urinary disorders

Subcapsular renal haematoma

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Reproductive system and breast disorders

Balanoposthitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Reproductive system and breast disorders

Benign prostatic hyperplasia

0.18%

5/2827 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.35%

10/2831 • Number of events 10 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Reproductive system and breast disorders

Dysfunctional uterine bleeding

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Reproductive system and breast disorders

Endometrial hyperplasia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Reproductive system and breast disorders

Metrorrhagia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Reproductive system and breast disorders

Ovarian cyst

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Reproductive system and breast disorders

Uterine haemorrhage

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Reproductive system and breast disorders

Uterine polyp

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Reproductive system and breast disorders

Vaginal haemorrhage

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Reproductive system and breast disorders

Prostatomegaly

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Reproductive system and breast disorders

Endometrial thickening

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Reproductive system and breast disorders

Testicular mass

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Acute pulmonary oedema

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure

0.21%

6/2827 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.53%

15/2831 • Number of events 18 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Aspiration

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Asthma

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.21%

6/2831 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Bronchitis chronic

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease

0.50%

14/2827 • Number of events 21 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.42%

12/2831 • Number of events 13 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Chronic respiratory failure

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Cough

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Dyspnoea

0.28%

8/2827 • Number of events 9 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.25%

7/2831 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Dyspnoea at rest

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Dyspnoea exertional

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Emphysema

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Epistaxis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Hypoxia

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Interstitial lung disease

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Laryngeal oedema

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Laryngeal stenosis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Pharyngeal oedema

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Pleural effusion

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Pleurisy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Pneumonia aspiration

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Pneumonitis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Pneumothorax

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Pulmonary congestion

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism

0.28%

8/2827 • Number of events 8 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Pulmonary hypertension

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Pulmonary oedema

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Respiratory distress

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Respiratory failure

0.18%

5/2827 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.25%

7/2831 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Sleep apnoea syndrome

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Vocal cord polyp

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Wheezing

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Restrictive pulmonary disease

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Vocal cord cyst

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Bronchopneumopathy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Pulmonary mass

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Laryngeal dysplasia

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Epiglottic cyst

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Laryngeal mass

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Pulmonary hilum mass

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Respiratory, thoracic and mediastinal disorders

Obstructive airways disorder

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Actinic keratosis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Angioedema

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Blister

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Decubitus ulcer

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Dermal cyst

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Dermatitis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Dermatitis allergic

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Dermatitis bullous

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Dermatitis herpetiformis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Drug eruption

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Ecchymosis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Eczema

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Hyperkeratosis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Ingrowing nail

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Parapsoriasis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Pemphigoid

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Purpura

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Rash

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Skin disorder

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Skin necrosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Skin ulcer

0.32%

9/2827 • Number of events 10 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.57%

16/2831 • Number of events 19 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Stasis dermatitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Stevens-Johnson syndrome

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Neuropathic ulcer

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Skin and subcutaneous tissue disorders

Diabetic foot

0.46%

13/2827 • Number of events 16 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.64%

18/2831 • Number of events 22 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Social circumstances

Social stay hospitalisation

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Aortic valve replacement

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Arteriovenous fistula operation

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Cardiac pacemaker insertion

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Cholecystectomy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Coronary artery bypass

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Foot amputation

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.11%

3/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Haemodialysis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Hip arthroplasty

0.11%

3/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.21%

6/2831 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Hysterectomy

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Insertion of ambulatory peritoneal catheter

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Knee arthroplasty

0.14%

4/2827 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.21%

6/2831 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Leg amputation

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Metatarsal excision

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Myomectomy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Nephrectomy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Parathyroidectomy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Physiotherapy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Pterygium operation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Rhinoplasty

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Spinal decompression

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Tenotomy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Toe amputation

0.14%

4/2827 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Transurethral prostatectomy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Umbilical hernia repair

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Uterine prolapse repair

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Vitrectomy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Lymphadenectomy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Cardiac pacemaker replacement

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Implantable defibrillator insertion

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Coronary angioplasty

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Spinal fusion surgery

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Radical prostatectomy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Diabetes mellitus management

0.11%

3/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Transurethral bladder resection

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Cardiac rehabilitation therapy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Continuous positive airway pressure

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Nephroureterectomy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Pancreaticosplenectomy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Polypectomy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Maxillofacial operation

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Corneal transplant

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Meniscus operation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Bladder neck operation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Urethral dilation procedure

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Intervertebral disc operation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Rehabilitation therapy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Dialysis device insertion

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Skin neoplasm excision

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Foot operation

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Amputation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Arthrodesis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Colectomy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Colon operation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Eye operation

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Oophorectomy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Prostatectomy

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Gastrectomy

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Gastric bypass

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Hydrocele operation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Intestinal operation

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Nail operation

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Skin graft

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Spinal operation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Wound treatment

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Bladder polypectomy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Cataract operation

0.14%

4/2827 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.42%

12/2831 • Number of events 14 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Aneurysm repair

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Bowel preparation

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Retinopexy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Intraocular lens implant

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Vascular graft

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Internal fixation of spine

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Bile duct stent removal

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Gastric banding reversal

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Therapeutic nerve ablation

0.04%

1/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Peripheral artery bypass

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Large intestinal polypectomy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Surgical and medical procedures

Metabolic surgery

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Aortic aneurysm

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Aortic dissection

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Aortic stenosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Arteriovenous fistula

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Blood pressure fluctuation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Circulatory collapse

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Embolism venous

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Haematoma

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Hypertension

0.53%

15/2827 • Number of events 16 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.81%

23/2831 • Number of events 26 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Hypertensive crisis

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.25%

7/2831 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Hypotension

0.25%

7/2827 • Number of events 7 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.18%

5/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Hypovolaemic shock

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Intermittent claudication

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Lymphoedema

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Malignant hypertension

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Orthostatic hypotension

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Peripheral ischaemia

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Peripheral vascular disorder

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Temporal arteritis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Thromboangiitis obliterans

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Thrombophlebitis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Thrombophlebitis superficial

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Thrombosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Shock haemorrhagic

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Dry gangrene

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Deep vein thrombosis

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Peripheral artery aneurysm

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Peripheral artery occlusion

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Hypertensive emergency

0.07%

2/2827 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.14%

4/2831 • Number of events 5 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Hypertensive urgency

0.14%

4/2827 • Number of events 4 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Venous occlusion

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Extremity necrosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Peripheral embolism

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Diabetic vascular disorder

0.07%

2/2827 • Number of events 2 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Microangiopathy

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Peripheral arterial occlusive disease

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.21%

6/2831 • Number of events 6 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Peripheral artery stenosis

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Vascular disorders

Peripheral artery thrombosis

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.04%

1/2831 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Product Issues

Device malfunction

0.04%

1/2827 • Number of events 1 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.00%

0/2831 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Product Issues

Device dislocation

0.00%

0/2827 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

0.07%

2/2831 • Number of events 3 • After the first dose of study drug up to 3 days after any temporary or permanent interruption of study drug, with an average treatment duration of 27 months

Adverse events are reported for the safety analysis set (SAF) that comprised all randomized subjects who took at least 1 dose of study drug. Adverse event reporting for the all-cause mortality considers all deaths in full analysis set (FAS, comprised all randomized participants except those with critical GCP violations) that occurred at any time during the study after randomization, including deaths after end of study visit (with an average study duration of 32 months).

Trial Outcomes & Findings for Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease (NCT NCT02540993)

Results Overview

Participant Flow

Participant milestones

Reasons for withdrawal

Baseline Characteristics

Baseline characteristics by cohort

PRIMARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

Adverse Events

Finerenone

Placebo

Serious adverse events

Other adverse events

Additional Information

Therapeutic Area Head

Results disclosure agreements