Trial Outcomes & Findings for Phase IIb Safety and Efficacy Study of Different Oral Doses of BAY94-8862 in Subjects With Worsening Chronic Heart Failure and Left Ventricular Systolic Dysfunction and Either Type 2 Diabetes Mellitus With or Without Chronic Kidney Disease or Chronic Kidney Disease Alone (NCT NCT01807221)

Last Updated: 2021-07-06

Results Overview

N-terminal pro-B type natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute and chronic heart failure (CHF) and may be useful to establish prognosis in heart failure.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

1066 participants

Primary outcome timeframe

Baseline and Day 90

Results posted on

2021-07-06

Participant Flow

Study was conducted in 168 study centers in 25 countries worldwide, from 17 June 2013 (first participant first visit) to 09 December 2014 (last participant last visit).

Out of 1286 screened participants, 1066 participants were randomized, 1055 participants received study treatment and were valid for safety analysis set.

Participant milestones

Participant milestones
Measure	Eplerenone (INSPRA®) Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone (BAY94-8862) 2.5-5 mg OD Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.
Overall Study STARTED	224	173	165	169	170	165
Overall Study Participants Received Study Treatment and Valid for Safety Analysis Set	221	172	163	167	169	163
Overall Study COMPLETED	144	121	122	123	134	124
Overall Study NOT COMPLETED	80	52	43	46	36	41

Reasons for withdrawal

Reasons for withdrawal
Measure	Eplerenone (INSPRA®) Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone (BAY94-8862) 2.5-5 mg OD Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.
Overall Study Progressive disease	1	0	1	0	0	0
Overall Study Death	7	9	4	2	1	6
Overall Study Physician Decision	2	1	0	0	0	0
Overall Study Adverse Event	33	22	26	25	18	21
Overall Study Protocol Violation	0	2	1	2	0	1
Overall Study Non-compliance	1	2	0	1	0	0
Overall Study Logistical difficulties	0	1	0	0	1	0
Overall Study Withdrawal by Subject	33	15	8	14	16	13
Overall Study Sponsor decision	2	0	1	1	0	0
Overall Study Lost to Follow-up	1	0	2	1	0	0

Baseline Characteristics

Participants with valid data for this baseline characteristic

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eplerenone (INSPRA®) n=221 Participants Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone (BAY94-8862) 2.5-5 mg OD n=172 Participants Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD n=163 Participants Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD n=167 Participants Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD n=169 Participants Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD n=163 Participants Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Total n=1055 Participants Total of all reporting groups
Age, Continuous	72.38 years STANDARD_DEVIATION 9.92 • n=221 Participants	72.53 years STANDARD_DEVIATION 9.74 • n=172 Participants	71.81 years STANDARD_DEVIATION 10.55 • n=163 Participants	69.27 years STANDARD_DEVIATION 9.83 • n=167 Participants	71.27 years STANDARD_DEVIATION 10.27 • n=169 Participants	69.2 years STANDARD_DEVIATION 10.15 • n=163 Participants	71.15 years STANDARD_DEVIATION 10.14 • n=1055 Participants
Sex: Female, Male Female	51 Participants n=221 Participants	37 Participants n=172 Participants	37 Participants n=163 Participants	43 Participants n=167 Participants	41 Participants n=169 Participants	31 Participants n=163 Participants	240 Participants n=1055 Participants
Sex: Female, Male Male	170 Participants n=221 Participants	135 Participants n=172 Participants	126 Participants n=163 Participants	124 Participants n=167 Participants	128 Participants n=169 Participants	132 Participants n=163 Participants	815 Participants n=1055 Participants
Baseline BNP	594.290 pg/ml STANDARD_DEVIATION 2.601 • n=203 Participants • Participants with valid data for this baseline characteristic	677.906 pg/ml STANDARD_DEVIATION 2.637 • n=156 Participants • Participants with valid data for this baseline characteristic	574.245 pg/ml STANDARD_DEVIATION 2.543 • n=151 Participants • Participants with valid data for this baseline characteristic	570.776 pg/ml STANDARD_DEVIATION 2.741 • n=156 Participants • Participants with valid data for this baseline characteristic	606.080 pg/ml STANDARD_DEVIATION 2.598 • n=158 Participants • Participants with valid data for this baseline characteristic	552.032 pg/ml STANDARD_DEVIATION 2.698 • n=155 Participants • Participants with valid data for this baseline characteristic	594.732 pg/ml STANDARD_DEVIATION 2.634 • n=979 Participants • Participants with valid data for this baseline characteristic
Baseline NT-proBNP	4730.170 pg/ml STANDARD_DEVIATION 2.938 • n=207 Participants • Participants with valid data for this baseline characteristic	4793.430 pg/ml STANDARD_DEVIATION 3.084 • n=162 Participants • Participants with valid data for this baseline characteristic	4184.631 pg/ml STANDARD_DEVIATION 3.093 • n=157 Participants • Participants with valid data for this baseline characteristic	3776.859 pg/ml STANDARD_DEVIATION 3.395 • n=158 Participants • Participants with valid data for this baseline characteristic	4163.898 pg/ml STANDARD_DEVIATION 2.734 • n=160 Participants • Participants with valid data for this baseline characteristic	3791.677 pg/ml STANDARD_DEVIATION 3.013 • n=158 Participants • Participants with valid data for this baseline characteristic	4246.883 pg/ml STANDARD_DEVIATION 3.040 • n=1002 Participants • Participants with valid data for this baseline characteristic

PRIMARY outcome

Timeframe: Baseline and Day 90

Population: Full analysis set (FAS): all participants who the study drug, had baseline and at least one post-baseline NT-proBNP value or who died or experienced permanent (≥5 consecutive days) withdrawal of study drug after cardiovascular (CV) hospitalization or after emergency presentation for Worsening Chronic Heart Failure (WCHF)

Outcome measures

Outcome measures
Measure	Eplerenone (INSPRA®) n=207 Participants Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone (BAY94-8862) 2.5-5 mg OD n=162 Participants Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD n=157 Participants Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD n=158 Participants Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD n=160 Participants Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD n=158 Participants Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.
Percentage of Participants With a Relative Decrease in NT-proBNP of More Than 30% From Baseline to Day 90	37.2 Percentage of participants 90% Confidence Interval 31.6 • Interval 31.6 to 43.1	30.9 Percentage of participants 90% Confidence Interval 24.9 • Interval 24.9 to 37.4	32.5 Percentage of participants 90% Confidence Interval 26.3 • Interval 26.3 to 39.2	37.3 Percentage of participants 90% Confidence Interval 30.9 • Interval 30.9 to 44.1	38.8 Percentage of participants 90% Confidence Interval 32.3 • Interval 32.3 to 45.5	34.2 Percentage of participants 90% Confidence Interval 27.9 • Interval 27.9 to 40.9

SECONDARY outcome

Timeframe: Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)

Population: Participants in FAS

Death due to any cause include cardiovascular (CV) death and Non-CV death. Non-CV death was classified by 2 subcategories: non-malignant causes and malignant causes.

Outcome measures

Outcome measures
Measure	Eplerenone (INSPRA®) n=207 Participants Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone (BAY94-8862) 2.5-5 mg OD n=162 Participants Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD n=157 Participants Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD n=158 Participants Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD n=160 Participants Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD n=158 Participants Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.
Number of Participants With Death Due to Any Cause Day 30	6 Participants	5 Participants	1 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Death Due to Any Cause Day 60	7 Participants	7 Participants	3 Participants	2 Participants	0 Participants	4 Participants
Number of Participants With Death Due to Any Cause Day 90	9 Participants	10 Participants	4 Participants	4 Participants	1 Participants	5 Participants
Number of Participants With Death Due to Any Cause Follow-up	15 Participants	16 Participants	7 Participants	11 Participants	2 Participants	8 Participants

SECONDARY outcome

Timeframe: Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)

Population: Participants in FAS

Hospitalizations were defined as any unplanned admission to hospital, i.e. completion of hospital admission procedures and one overnight \[i.e. date change\] stay or until the death of subject occurred. Hospitalizations and deaths were classified by 2 primary categories: CV and non-CV. The pre-specified subcategories for CV hospitalizations were as follows: 1. Worsening heart failure, 2.Acute myocardial infarction, 3. Arrhythmia, 4.Transient ischemic attack and stroke, 5. Other CV hospitalizations.

Outcome measures

Outcome measures
Measure	Eplerenone (INSPRA®) n=207 Participants Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone (BAY94-8862) 2.5-5 mg OD n=162 Participants Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD n=157 Participants Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD n=158 Participants Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD n=160 Participants Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD n=158 Participants Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.
Number of Participants With Cardiovascular Hospitalization Day 60	43 Participants	33 Participants	23 Participants	21 Participants	15 Participants	23 Participants
Number of Participants With Cardiovascular Hospitalization Follow-up	56 Participants	43 Participants	38 Participants	36 Participants	27 Participants	34 Participants
Number of Participants With Cardiovascular Hospitalization Day 30	28 Participants	23 Participants	14 Participants	8 Participants	7 Participants	15 Participants
Number of Participants With Cardiovascular Hospitalization Day 90	45 Participants	35 Participants	26 Participants	29 Participants	22 Participants	28 Participants

SECONDARY outcome

Timeframe: Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)

Population: Participants in FAS

Emergency presentations for WCHF were defined as newly developing signs and symptoms of WCHF after start of treatment with study drug, requiring an additional emergency presentation to hospital and IV treatment with diuretics and/or positive inotropic agents.

Outcome measures

Outcome measures
Measure	Eplerenone (INSPRA®) n=207 Participants Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone (BAY94-8862) 2.5-5 mg OD n=162 Participants Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD n=157 Participants Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD n=158 Participants Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD n=160 Participants Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD n=158 Participants Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.
Number of Participants With Emergency Presentations for Worsening Chronic Heart Failure (WCHF) Day 90	37 Participants	32 Participants	22 Participants	24 Participants	18 Participants	28 Participants
Number of Participants With Emergency Presentations for Worsening Chronic Heart Failure (WCHF) Follow-up	47 Participants	40 Participants	30 Participants	30 Participants	26 Participants	34 Participants
Number of Participants With Emergency Presentations for Worsening Chronic Heart Failure (WCHF) Day 30	21 Participants	19 Participants	12 Participants	9 Participants	7 Participants	15 Participants
Number of Participants With Emergency Presentations for Worsening Chronic Heart Failure (WCHF) Day 60	35 Participants	30 Participants	20 Participants	17 Participants	14 Participants	22 Participants

SECONDARY outcome

Timeframe: Day 30, Day 60, Day 90, Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120)

Population: Participants in FAS with valid data at specified visits

B-type natriuretic peptide (BNP) levels in the blood are used for screening, diagnosis of acute chronic heart failure (CHF) and may be useful to establish prognosis in heart failure.

Outcome measures

Outcome measures
Measure	Eplerenone (INSPRA®) n=203 Participants Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone (BAY94-8862) 2.5-5 mg OD n=156 Participants Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD n=151 Participants Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD n=156 Participants Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD n=158 Participants Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD n=155 Participants Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.
Ratio of BNP at Specified Visits to BNP at Baseline Day 30	0.925 Ratio Standard Deviation 2.02	0.944 Ratio Standard Deviation 1.952	0.878 Ratio Standard Deviation 1.713	0.832 Ratio Standard Deviation 1.959	0.852 Ratio Standard Deviation 1.901	0.879 Ratio Standard Deviation 1.968
Ratio of BNP at Specified Visits to BNP at Baseline Day 60	0.783 Ratio Standard Deviation 2.194	0.864 Ratio Standard Deviation 2.139	0.854 Ratio Standard Deviation 1.854	0.79 Ratio Standard Deviation 2.179	0.711 Ratio Standard Deviation 2.116	0.824 Ratio Standard Deviation 2.142
Ratio of BNP at Specified Visits to BNP at Baseline Day 90	0.723 Ratio Standard Deviation 2.202	0.813 Ratio Standard Deviation 2.412	0.839 Ratio Standard Deviation 1.93	0.719 Ratio Standard Deviation 2.204	0.706 Ratio Standard Deviation 2.34	0.771 Ratio Standard Deviation 2.197
Ratio of BNP at Specified Visits to BNP at Baseline Premature discontinuation	0.896 Ratio Standard Deviation 0.896	1.104 Ratio Standard Deviation 2.15	1.006 Ratio Standard Deviation 2.422	0.884 Ratio Standard Deviation 1.973	0.848 Ratio Standard Deviation 2.218	1.044 Ratio Standard Deviation 2.174
Ratio of BNP at Specified Visits to BNP at Baseline Follow-up	0.795 Ratio Standard Deviation 2.232	0.815 Ratio Standard Deviation 2.388	0.886 Ratio Standard Deviation 2.199	0.726 Ratio Standard Deviation 2.397	0.729 Ratio Standard Deviation 2.487	0.852 Ratio Standard Deviation 2.169

SECONDARY outcome

Population: Participants in FAS with valid data at specified visits

N-terminal pro-B type natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute chronic heart failure (CHF) and may be useful to establish prognosis in heart failure.

Outcome measures

Outcome measures
Measure	Eplerenone (INSPRA®) n=207 Participants Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone (BAY94-8862) 2.5-5 mg OD n=162 Participants Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD n=157 Participants Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD n=158 Participants Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD n=160 Participants Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD n=158 Participants Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.
Ratio of NT-proBNP at Specified Visits to NT-proBNP at Baseline Day 60	0.749 Ratio Standard Deviation 2.73	0.822 Ratio Standard Deviation 2.423	0.814 Ratio Standard Deviation 2.178	0.81 Ratio Standard Deviation 2.268	0.748 Ratio Standard Deviation 2.496	0.829 Ratio Standard Deviation 2.288
Ratio of NT-proBNP at Specified Visits to NT-proBNP at Baseline Follow-up	0.747 Ratio Standard Deviation 2.616	0.747 Ratio Standard Deviation 2.741	0.887 Ratio Standard Deviation 2.604	0.809 Ratio Standard Deviation 2.647	0.746 Ratio Standard Deviation 2.472	0.849 Ratio Standard Deviation 2.348
Ratio of NT-proBNP at Specified Visits to NT-proBNP at Baseline Day 30	0.883 Ratio Standard Deviation 2.458	0.98 Ratio Standard Deviation 2.158	0.874 Ratio Standard Deviation 2.14	0.888 Ratio Standard Deviation 2.123	0.822 Ratio Standard Deviation 2.217	0.921 Ratio Standard Deviation 2.136
Ratio of NT-proBNP at Specified Visits to NT-proBNP at Baseline Day 90	0.688 Ratio Standard Deviation 2.59	0.789 Ratio Standard Deviation 2.661	0.765 Ratio Standard Deviation 2.214	0.783 Ratio Standard Deviation 2.454	0.728 Ratio Standard Deviation 2.795	0.771 Ratio Standard Deviation 2.471
Ratio of NT-proBNP at Specified Visits to NT-proBNP at Baseline Premature discontinuation	0.948 Ratio Standard Deviation 2.684	1.369 Ratio Standard Deviation 2.087	1.267 Ratio Standard Deviation 2.261	0.927 Ratio Standard Deviation 1.864	1.133 Ratio Standard Deviation 2.981	0.965 Ratio Standard Deviation 2.352

SECONDARY outcome

Timeframe: Baseline, Day 30 and Day 90

Population: Participants in FAS with valid data at specified visits

The Kansas City Cardiomyopathy Questionnaire (KCCQ) was the leading health related quality of life measure for subjects with CHF. KCCQ was a 23 item questionnaire that independently measures the impact of subjects HF, or its treatment, on 7 distinct domains: self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. KCCQ clinical summary score is a composite assessment of physical limitations and total symptom scores. Results from the total symptom summary score are presented. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. In the below table, categorical data represents change from baseline data at respective time points.

Outcome measures

Outcome measures
Measure	Eplerenone (INSPRA®) n=203 Participants Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone (BAY94-8862) 2.5-5 mg OD n=161 Participants Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD n=156 Participants Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD n=158 Participants Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD n=160 Participants Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD n=157 Participants Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.
Change From Baseline in KCCQ Questionnaire Scores at Specified Visits Baseline	43.7 Scores on a scale Standard Deviation 23	42.8 Scores on a scale Standard Deviation 22.6	45.4 Scores on a scale Standard Deviation 24	42.1 Scores on a scale Standard Deviation 23.2	42.3 Scores on a scale Standard Deviation 23.7	43.2 Scores on a scale Standard Deviation 22.5
Change From Baseline in KCCQ Questionnaire Scores at Specified Visits Day 30	20.5 Scores on a scale Standard Deviation 26.2	18.2 Scores on a scale Standard Deviation 22.7	19.3 Scores on a scale Standard Deviation 26.5	23 Scores on a scale Standard Deviation 24.4	24.9 Scores on a scale Standard Deviation 22.9	20.6 Scores on a scale Standard Deviation 27
Change From Baseline in KCCQ Questionnaire Scores at Specified Visits Day 90	24.3 Scores on a scale Standard Deviation 27.6	21.3 Scores on a scale Standard Deviation 27.2	24.5 Scores on a scale Standard Deviation 27	29.3 Scores on a scale Standard Deviation 28.6	28.3 Scores on a scale Standard Deviation 23.8	22.2 Scores on a scale Standard Deviation 30.6

SECONDARY outcome

Timeframe: Baseline, Day 30, Day 90, Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120)

Population: Participants in FAS with valid data at specified visits

EuroQol Group 5-Dimension, 3-Level (EQ-5D-3L): participant rated questionnaire to assess health-related quality of life. It consists of EQ-5D descriptive system and EQ-5D Visual Analog Scale (VAS). EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems (1), some problems (2), and extreme problems (3). For this population, the possible EQ-5D-3L index scores ranges from -0.11 (that is, 3 for all 5 dimensions) to 1.0 (that is, 1 for all 5 dimensions), where higher scores indicate a better health state.

Outcome measures

Outcome measures
Measure	Eplerenone (INSPRA®) n=207 Participants Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone (BAY94-8862) 2.5-5 mg OD n=162 Participants Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD n=157 Participants Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD n=158 Participants Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD n=160 Participants Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD n=158 Participants Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.
Change From Baseline in EQ-5D-3L Questionnaire Scores at Specified Visits Premature discontinuation	-0.12 Scores on scale Standard Deviation 0.25	-0.06 Scores on scale Standard Deviation 0.29	-0.09 Scores on scale Standard Deviation 0.24	-0.1 Scores on scale Standard Deviation 0.24	-0.05 Scores on scale Standard Deviation 0.25	0 Scores on scale Standard Deviation 0.29
Change From Baseline in EQ-5D-3L Questionnaire Scores at Specified Visits Follow-up	0.06 Scores on scale Standard Deviation 0.26	0.01 Scores on scale Standard Deviation 0.25	0.01 Scores on scale Standard Deviation 0.27	0.08 Scores on scale Standard Deviation 0.23	0.07 Scores on scale Standard Deviation 0.23	0.04 Scores on scale Standard Deviation 0.28
Change From Baseline in EQ-5D-3L Questionnaire Scores at Specified Visits Baseline	0.58 Scores on scale Standard Deviation 0.25	0.59 Scores on scale Standard Deviation 0.25	0.62 Scores on scale Standard Deviation 0.23	0.58 Scores on scale Standard Deviation 0.23	0.56 Scores on scale Standard Deviation 0.25	0.59 Scores on scale Standard Deviation 0.24
Change From Baseline in EQ-5D-3L Questionnaire Scores at Specified Visits Day 30	0.06 Scores on scale Standard Deviation 0.23	0.02 Scores on scale Standard Deviation 0.24	0.02 Scores on scale Standard Deviation 0.23	0.07 Scores on scale Standard Deviation 0.22	0.06 Scores on scale Standard Deviation 0.23	0.02 Scores on scale Standard Deviation 0.25
Change From Baseline in EQ-5D-3L Questionnaire Scores at Specified Visits Day 90	0.08 Scores on scale Standard Deviation 0.24	0.03 Scores on scale Standard Deviation 0.27	0.04 Scores on scale Standard Deviation 0.25	0.08 Scores on scale Standard Deviation 0.2	0.1 Scores on scale Standard Deviation 0.24	0.06 Scores on scale Standard Deviation 0.28

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)

Population: Participants in SAF with valid data at specified visits

Outcome measures

Outcome measures
Measure	Eplerenone (INSPRA®) n=221 Participants Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone (BAY94-8862) 2.5-5 mg OD n=172 Participants Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD n=162 Participants Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD n=167 Participants Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD n=168 Participants Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD n=163 Participants Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.
Change From Baseline in Serum Potassium at Specified Visits Baseline	4.159 millimoles per liter (mmol/L) Standard Deviation 0.495	4.081 millimoles per liter (mmol/L) Standard Deviation 0.501	4.211 millimoles per liter (mmol/L) Standard Deviation 0.541	4.174 millimoles per liter (mmol/L) Standard Deviation 0.443	4.131 millimoles per liter (mmol/L) Standard Deviation 0.506	4.117 millimoles per liter (mmol/L) Standard Deviation 0.506
Change From Baseline in Serum Potassium at Specified Visits Day 30	0.057 millimoles per liter (mmol/L) Standard Deviation 0.608	0.135 millimoles per liter (mmol/L) Standard Deviation 0.573	0.075 millimoles per liter (mmol/L) Standard Deviation 0.523	0.085 millimoles per liter (mmol/L) Standard Deviation 0.475	0.21 millimoles per liter (mmol/L) Standard Deviation 0.592	0.193 millimoles per liter (mmol/L) Standard Deviation 0.556
Change From Baseline in Serum Potassium at Specified Visits Day 60	0.179 millimoles per liter (mmol/L) Standard Deviation 0.589	0.091 millimoles per liter (mmol/L) Standard Deviation 0.568	0.131 millimoles per liter (mmol/L) Standard Deviation 0.566	0.171 millimoles per liter (mmol/L) Standard Deviation 0.54	0.274 millimoles per liter (mmol/L) Standard Deviation 0.522	0.216 millimoles per liter (mmol/L) Standard Deviation 0.547
Change From Baseline in Serum Potassium at Specified Visits Day 90	0.307 millimoles per liter (mmol/L) Standard Deviation 0.609	0.184 millimoles per liter (mmol/L) Standard Deviation 0.574	0.153 millimoles per liter (mmol/L) Standard Deviation 0.516	0.164 millimoles per liter (mmol/L) Standard Deviation 0.579	0.275 millimoles per liter (mmol/L) Standard Deviation 0.58	0.245 millimoles per liter (mmol/L) Standard Deviation 0.574
Change From Baseline in Serum Potassium at Specified Visits Follow-up	0.117 millimoles per liter (mmol/L) Standard Deviation 0.621	0.226 millimoles per liter (mmol/L) Standard Deviation 0.694	0.054 millimoles per liter (mmol/L) Standard Deviation 0.623	0.05 millimoles per liter (mmol/L) Standard Deviation 0.572	0.175 millimoles per liter (mmol/L) Standard Deviation 0.559	0.036 millimoles per liter (mmol/L) Standard Deviation 0.556

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline,Day 7,14,30,60,90,Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120)

Population: Participants in SAF with valid data at specified visits

Outcome measures

Outcome measures
Measure	Eplerenone (INSPRA®) n=218 Participants Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone (BAY94-8862) 2.5-5 mg OD n=171 Participants Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD n=160 Participants Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD n=165 Participants Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD n=169 Participants Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD n=163 Participants Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.
Change From Baseline in Systolic Blood Pressure at Specified Visits Day 7	-0.541 millimeter of mercury (mmHg) Standard Deviation 13.894	-3.178 millimeter of mercury (mmHg) Standard Deviation 13.72	-2.565 millimeter of mercury (mmHg) Standard Deviation 12.278	0.568 millimeter of mercury (mmHg) Standard Deviation 12.733	0.162 millimeter of mercury (mmHg) Standard Deviation 15.416	-0.546 millimeter of mercury (mmHg) Standard Deviation 13.498
Change From Baseline in Systolic Blood Pressure at Specified Visits Day 14	-3.442 millimeter of mercury (mmHg) Standard Deviation 14.258	-4.488 millimeter of mercury (mmHg) Standard Deviation 10.31	4.142 millimeter of mercury (mmHg) Standard Deviation 15.001	1.241 millimeter of mercury (mmHg) Standard Deviation 13.561	-3.099 millimeter of mercury (mmHg) Standard Deviation 12.591	-2.906 millimeter of mercury (mmHg) Standard Deviation 15.406
Change From Baseline in Systolic Blood Pressure at Specified Visits Day 30	0.067 millimeter of mercury (mmHg) Standard Deviation 15.312	-0.824 millimeter of mercury (mmHg) Standard Deviation 15.747	-0.367 millimeter of mercury (mmHg) Standard Deviation 14.984	0.374 millimeter of mercury (mmHg) Standard Deviation 14.433	1.786 millimeter of mercury (mmHg) Standard Deviation 15.039	0.899 millimeter of mercury (mmHg) Standard Deviation 14.608
Change From Baseline in Systolic Blood Pressure at Specified Visits Baseline	120.554 millimeter of mercury (mmHg) Standard Deviation 18.706	119.492 millimeter of mercury (mmHg) Standard Deviation 16.348	118.498 millimeter of mercury (mmHg) Standard Deviation 14.355	119.087 millimeter of mercury (mmHg) Standard Deviation 16.677	116.024 millimeter of mercury (mmHg) Standard Deviation 16.895	116.941 millimeter of mercury (mmHg) Standard Deviation 16.548
Change From Baseline in Systolic Blood Pressure at Specified Visits Day 60	0.684 millimeter of mercury (mmHg) Standard Deviation 16.315	0.337 millimeter of mercury (mmHg) Standard Deviation 14.176	-1.249 millimeter of mercury (mmHg) Standard Deviation 13.659	-1.811 millimeter of mercury (mmHg) Standard Deviation 14.462	0.981 millimeter of mercury (mmHg) Standard Deviation 15.525	0.667 millimeter of mercury (mmHg) Standard Deviation 14.83
Change From Baseline in Systolic Blood Pressure at Specified Visits Day 90	-0.967 millimeter of mercury (mmHg) Standard Deviation 16.408	0.922 millimeter of mercury (mmHg) Standard Deviation 15.847	0.047 millimeter of mercury (mmHg) Standard Deviation 15.643	-0.664 millimeter of mercury (mmHg) Standard Deviation 15.018	1.216 millimeter of mercury (mmHg) Standard Deviation 17.831	0.956 millimeter of mercury (mmHg) Standard Deviation 15.743
Change From Baseline in Systolic Blood Pressure at Specified Visits Premature discontinuation	-2.991 millimeter of mercury (mmHg) Standard Deviation 16.456	-0.41 millimeter of mercury (mmHg) Standard Deviation 13.936	-2.167 millimeter of mercury (mmHg) Standard Deviation 19.963	9.391 millimeter of mercury (mmHg) Standard Deviation 22.378	-2.32 millimeter of mercury (mmHg) Standard Deviation 11.963	-0.028 millimeter of mercury (mmHg) Standard Deviation 15.42
Change From Baseline in Systolic Blood Pressure at Specified Visits Follow-up	0.188 millimeter of mercury (mmHg) Standard Deviation 16.751	2.869 millimeter of mercury (mmHg) Standard Deviation 15.502	1.95 millimeter of mercury (mmHg) Standard Deviation 16.148	-0.928 millimeter of mercury (mmHg) Standard Deviation 17.953	2.041 millimeter of mercury (mmHg) Standard Deviation 16.189	3.037 millimeter of mercury (mmHg) Standard Deviation 16.782

OTHER_PRE_SPECIFIED outcome

Population: Participants in SAF with valid data at specified visits

Outcome measures

Outcome measures
Measure	Eplerenone (INSPRA®) n=218 Participants Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone (BAY94-8862) 2.5-5 mg OD n=171 Participants Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD n=160 Participants Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD n=165 Participants Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD n=169 Participants Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD n=163 Participants Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.
Change From Baseline in Diastolic Blood Pressure at Specified Visits Day 7	-1.351 millimeter for mercury (mmHg) Standard Deviation 10.237	-1.693 millimeter for mercury (mmHg) Standard Deviation 9.911	-2.143 millimeter for mercury (mmHg) Standard Deviation 9.848	0.013 millimeter for mercury (mmHg) Standard Deviation 9.733	-0.738 millimeter for mercury (mmHg) Standard Deviation 10.534	-1.166 millimeter for mercury (mmHg) Standard Deviation 8.964
Change From Baseline in Diastolic Blood Pressure at Specified Visits Day 30	-0.503 millimeter for mercury (mmHg) Standard Deviation 10.826	0.146 millimeter for mercury (mmHg) Standard Deviation 10.667	-0.845 millimeter for mercury (mmHg) Standard Deviation 8.91	-0.068 millimeter for mercury (mmHg) Standard Deviation 9.633	-0.094 millimeter for mercury (mmHg) Standard Deviation 10.086	-1.163 millimeter for mercury (mmHg) Standard Deviation 9.622
Change From Baseline in Diastolic Blood Pressure at Specified Visits Day 60	-0.613 millimeter for mercury (mmHg) Standard Deviation 11.096	-0.199 millimeter for mercury (mmHg) Standard Deviation 11.297	-2.144 millimeter for mercury (mmHg) Standard Deviation 9.552	-0.85 millimeter for mercury (mmHg) Standard Deviation 10.472	0.17 millimeter for mercury (mmHg) Standard Deviation 10.312	-0.575 millimeter for mercury (mmHg) Standard Deviation 10.427
Change From Baseline in Diastolic Blood Pressure at Specified Visits Baseline	71.633 millimeter for mercury (mmHg) Standard Deviation 11.647	71.044 millimeter for mercury (mmHg) Standard Deviation 10.762	71.442 millimeter for mercury (mmHg) Standard Deviation 8.508	70.61 millimeter for mercury (mmHg) Standard Deviation 9.692	70.343 millimeter for mercury (mmHg) Standard Deviation 10.394	71.145 millimeter for mercury (mmHg) Standard Deviation 9.809
Change From Baseline in Diastolic Blood Pressure at Specified Visits Day 14	-3.442 millimeter for mercury (mmHg) Standard Deviation 10.089	-0.537 millimeter for mercury (mmHg) Standard Deviation 9.59	1.608 millimeter for mercury (mmHg) Standard Deviation 9.423	-0.083 millimeter for mercury (mmHg) Standard Deviation 7.421	-2.387 millimeter for mercury (mmHg) Standard Deviation 10.51	-0.625 millimeter for mercury (mmHg) Standard Deviation 9.41
Change From Baseline in Diastolic Blood Pressure at Specified Visits Day 90	-0.716 millimeter for mercury (mmHg) Standard Deviation 11.035	-0.106 millimeter for mercury (mmHg) Standard Deviation 11.148	-1.738 millimeter for mercury (mmHg) Standard Deviation 9.015	-1.121 millimeter for mercury (mmHg) Standard Deviation 9.96	-0.545 millimeter for mercury (mmHg) Standard Deviation 11.212	-0.877 millimeter for mercury (mmHg) Standard Deviation 11.327
Change From Baseline in Diastolic Blood Pressure at Specified Visits Premature discontinuation	-3.185 millimeter for mercury (mmHg) Standard Deviation 11.853	0.868 millimeter for mercury (mmHg) Standard Deviation 9.239	-2.194 millimeter for mercury (mmHg) Standard Deviation 15.522	4.101 millimeter for mercury (mmHg) Standard Deviation 12.151	-2.96 millimeter for mercury (mmHg) Standard Deviation 9.199	-0.083 millimeter for mercury (mmHg) Standard Deviation 10.113
Change From Baseline in Diastolic Blood Pressure at Specified Visits Follow-up	-1.218 millimeter for mercury (mmHg) Standard Deviation 11.477	0.696 millimeter for mercury (mmHg) Standard Deviation 13.172	-0.444 millimeter for mercury (mmHg) Standard Deviation 10.197	-1.16 millimeter for mercury (mmHg) Standard Deviation 11.114	-0.298 millimeter for mercury (mmHg) Standard Deviation 11.521	-0.172 millimeter for mercury (mmHg) Standard Deviation 10.211

OTHER_PRE_SPECIFIED outcome

Population: Participants in SAF with valid data at specified visits

Outcome measures

Outcome measures
Measure	Eplerenone (INSPRA®) n=217 Participants Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone (BAY94-8862) 2.5-5 mg OD n=171 Participants Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD n=160 Participants Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD n=165 Participants Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD n=169 Participants Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD n=162 Participants Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.
Change From Baseline in Heart Rate at Specified Visits Baseline	74.957 Beats per minute (Beats/min) Standard Deviation 13.813	73.369 Beats per minute (Beats/min) Standard Deviation 13.396	72.681 Beats per minute (Beats/min) Standard Deviation 12.623	74.184 Beats per minute (Beats/min) Standard Deviation 12.369	73.852 Beats per minute (Beats/min) Standard Deviation 11.999	74.329 Beats per minute (Beats/min) Standard Deviation 13.187
Change From Baseline in Heart Rate at Specified Visits Day 90	-0.189 Beats per minute (Beats/min) Standard Deviation 12.289	-1.647 Beats per minute (Beats/min) Standard Deviation 13.001	-2.89 Beats per minute (Beats/min) Standard Deviation 12.034	-2.212 Beats per minute (Beats/min) Standard Deviation 12.041	-0.71 Beats per minute (Beats/min) Standard Deviation 13.777	-1.145 Beats per minute (Beats/min) Standard Deviation 14.284
Change From Baseline in Heart Rate at Specified Visits Follow-up	-1.281 Beats per minute (Beats/min) Standard Deviation 13.789	-2.057 Beats per minute (Beats/min) Standard Deviation 13.982	-0.626 Beats per minute (Beats/min) Standard Deviation 14.196	-1.326 Beats per minute (Beats/min) Standard Deviation 15.488	0.834 Beats per minute (Beats/min) Standard Deviation 14.159	-1.317 Beats per minute (Beats/min) Standard Deviation 14.636
Change From Baseline in Heart Rate at Specified Visits Day 7	-0.8 Beats per minute (Beats/min) Standard Deviation 10.751	1.073 Beats per minute (Beats/min) Standard Deviation 13.5	-0.63 Beats per minute (Beats/min) Standard Deviation 11.696	-0.719 Beats per minute (Beats/min) Standard Deviation 10.77	-0.548 Beats per minute (Beats/min) Standard Deviation 11.144	-1.176 Beats per minute (Beats/min) Standard Deviation 13.398
Change From Baseline in Heart Rate at Specified Visits Day 14	-3.109 Beats per minute (Beats/min) Standard Deviation 15.101	0.599 Beats per minute (Beats/min) Standard Deviation 16.387	1.842 Beats per minute (Beats/min) Standard Deviation 14.988	-1.324 Beats per minute (Beats/min) Standard Deviation 13.666	0.423 Beats per minute (Beats/min) Standard Deviation 11.247	-3.969 Beats per minute (Beats/min) Standard Deviation 13.715
Change From Baseline in Heart Rate at Specified Visits Day 30	0.294 Beats per minute (Beats/min) Standard Deviation 13.61	1.064 Beats per minute (Beats/min) Standard Deviation 14.128	0.435 Beats per minute (Beats/min) Standard Deviation 13.63	-0.349 Beats per minute (Beats/min) Standard Deviation 12.636	-0.802 Beats per minute (Beats/min) Standard Deviation 11.311	-1.633 Beats per minute (Beats/min) Standard Deviation 12.719
Change From Baseline in Heart Rate at Specified Visits Day 60	0.297 Beats per minute (Beats/min) Standard Deviation 13.033	-0.975 Beats per minute (Beats/min) Standard Deviation 14.953	-1.741 Beats per minute (Beats/min) Standard Deviation 10.86	-2.318 Beats per minute (Beats/min) Standard Deviation 14.225	0.192 Beats per minute (Beats/min) Standard Deviation 13.377	-1.608 Beats per minute (Beats/min) Standard Deviation 13.828
Change From Baseline in Heart Rate at Specified Visits Premature discontinuation	-2.278 Beats per minute (Beats/min) Standard Deviation 15.909	-1.424 Beats per minute (Beats/min) Standard Deviation 15.587	-0.222 Beats per minute (Beats/min) Standard Deviation 7.591	1.101 Beats per minute (Beats/min) Standard Deviation 10.22	4.733 Beats per minute (Beats/min) Standard Deviation 13.646	-2.072 Beats per minute (Beats/min) Standard Deviation 19.731

Adverse Events

Eplerenone (INSPRA®)

Serious events: 77 serious events

Other events: 85 other events

Deaths: 19 deaths

Finerenone(BAY94-8862) 2.5-5 mg OD

Serious events: 72 serious events

Other events: 63 other events

Deaths: 17 deaths

Finerenone (BAY94-8862) 5-10 mg OD

Serious events: 47 serious events

Other events: 59 other events

Deaths: 9 deaths

Finerenone (BAY94-8862) 7.5-15 mg OD

Serious events: 52 serious events

Other events: 50 other events

Deaths: 12 deaths

Finerenone (BAY94-8862) 10-20 mg OD

Serious events: 46 serious events

Other events: 50 other events

Deaths: 2 deaths

Finerenone (BAY94-8862) 15-20 mg OD

Serious events: 57 serious events

Other events: 65 other events

Deaths: 9 deaths

Serious adverse events

Serious adverse events
Measure	Eplerenone (INSPRA®) n=221 participants at risk Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone(BAY94-8862) 2.5-5 mg OD n=172 participants at risk Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo-matched to Eplerenone capsule OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD n=163 participants at risk Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD n=167 participants at risk Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD n=169 participants at risk Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD n=163 participants at risk Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.
General disorders Stent-graft endoleak	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Hepatobiliary disorders Acute hepatic failure	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Vascular disorders Peripheral ischaemia	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Blood and lymphatic system disorders Anaemia	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Acute myocardial infarction	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Angina pectoris	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Atrial fibrillation	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/169 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Atrial flutter	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Atrial tachycardia	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Atrioventricular block complete	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Cardiac arrest	1.4% 3/221 • Number of events 3 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/163 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Cardiac failure	9.5% 21/221 • Number of events 27 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	9.3% 16/172 • Number of events 26 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	9.2% 15/163 • Number of events 17 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	12.6% 21/167 • Number of events 33 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	6.5% 11/169 • Number of events 12 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	8.0% 13/163 • Number of events 14 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Cardiac failure acute	2.7% 6/221 • Number of events 6 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.5% 6/172 • Number of events 6 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.8% 3/163 • Number of events 3 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.8% 3/169 • Number of events 4 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.1% 5/163 • Number of events 5 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Cardiac failure chronic	5.9% 13/221 • Number of events 16 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	5.2% 9/172 • Number of events 11 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.3% 7/163 • Number of events 7 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.8% 8/167 • Number of events 9 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.6% 6/169 • Number of events 6 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	7.4% 12/163 • Number of events 16 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Cardiac failure congestive	1.8% 4/221 • Number of events 5 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	2.9% 5/172 • Number of events 5 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/163 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/167 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.8% 3/163 • Number of events 7 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Cardiogenic shock	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Coronary artery disease	0.90% 2/221 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Coronary artery occlusion	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Coronary artery stenosis	0.45% 1/221 • Number of events 3 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Left ventricular failure	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Mitral valve incompetence	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Myocardial infarction	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Myocardial ischaemia	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Pericardial haemorrhage	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Right ventricular failure	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Sick sinus syndrome	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Supraventricular tachycardia	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Ventricular arrhythmia	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Ventricular fibrillation	1.4% 3/221 • Number of events 3 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.7% 3/172 • Number of events 4 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Ventricular tachycardia	0.90% 2/221 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	2.3% 4/172 • Number of events 8 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.8% 3/167 • Number of events 5 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Left ventricular dysfunction	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Cardiopulmonary failure	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Acute coronary syndrome	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Cardiac ventricular thrombosis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Ventricular tachyarrhythmia	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Cardiac disorders Cardiovascular insufficiency	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Endocrine disorders Hyperthyroidism	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Eye disorders Cataract	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Eye disorders Cataract nuclear	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Eye disorders Vitreous haemorrhage	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Gastrointestinal disorders Constipation	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Gastrointestinal disorders Diarrhoea	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Gastrointestinal disorders Gastritis erosive	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Gastrointestinal disorders Inguinal hernia	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Gastrointestinal disorders Pancreatitis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Gastrointestinal disorders Small intestinal perforation	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Gastrointestinal disorders Intestinal haemorrhage	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
General disorders Chest pain	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
General disorders Malaise	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
General disorders Pyrexia	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
General disorders Sudden death	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/172 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
General disorders Sudden cardiac death	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/163 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
General disorders Oedema due to cardiac disease	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
General disorders Implant site haematoma	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
General disorders Implant site ulcer	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Hepatobiliary disorders Hepatitis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Bronchitis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Bronchopneumonia	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Cellulitis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/163 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Endocarditis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Erysipelas	0.90% 2/221 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Gastrointestinal infection	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Infection	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Lymphangitis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Necrotising fasciitis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Osteomyelitis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Pneumonia	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.7% 3/172 • Number of events 3 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.8% 3/163 • Number of events 3 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/169 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.8% 3/163 • Number of events 3 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Pneumonia legionella	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Sepsis	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/167 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/169 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Septic shock	0.90% 2/221 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Upper respiratory tract infection	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Urinary tract infection	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Rectal abscess	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Staphylococcal bacteraemia	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Pneumococcal sepsis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Asymptomatic bacteriuria	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Escherichia infection	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Respiratory tract infection viral	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Respiratory tract infection	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Infections and infestations Enterocolitis bacterial	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Injury, poisoning and procedural complications Accident	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Injury, poisoning and procedural complications Incisional hernia	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Injury, poisoning and procedural complications Overdose	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Injury, poisoning and procedural complications Subdural haematoma	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Injury, poisoning and procedural complications Contusion	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Injury, poisoning and procedural complications Brain contusion	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Injury, poisoning and procedural complications Allergic transfusion reaction	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Injury, poisoning and procedural complications Toxicity to various agents	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Investigations Blood creatinine increased	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Investigations Blood potassium increased	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/163 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/163 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Investigations International normalised ratio increased	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Investigations Computerised tomogram abdomen abnormal	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Investigations Troponin T increased	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Investigations Hepatic enzyme increased	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Metabolism and nutrition disorders Dehydration	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Metabolism and nutrition disorders Diabetes mellitus	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Metabolism and nutrition disorders Hyperkalaemia	2.3% 5/221 • Number of events 5 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.5% 6/172 • Number of events 6 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	2.5% 4/163 • Number of events 4 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.2% 7/167 • Number of events 7 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.0% 5/169 • Number of events 5 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.7% 6/163 • Number of events 6 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Metabolism and nutrition disorders Hypoglycaemia	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/163 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/169 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Metabolism and nutrition disorders Hypovolaemia	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Musculoskeletal and connective tissue disorders Muscle haemorrhage	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenocarcinoma	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Vascular disorders Orthostatic hypotension	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Nervous system disorders Cerebellar syndrome	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Nervous system disorders Cerebrovascular accident	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Nervous system disorders Dizziness	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Nervous system disorders Embolic stroke	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Nervous system disorders Haemorrhage intracranial	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Nervous system disorders Loss of consciousness	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Nervous system disorders Nervous system disorder	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Nervous system disorders Status epilepticus	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Nervous system disorders Syncope	0.90% 2/221 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Nervous system disorders Vocal cord paralysis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Nervous system disorders Cerebrovascular insufficiency	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Nervous system disorders Ischaemic stroke	0.90% 2/221 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Psychiatric disorders Completed suicide	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Psychiatric disorders Delirium	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Psychiatric disorders Sleep disorder	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Psychiatric disorders Mental status changes	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Psychiatric disorders Psychotic disorder	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Renal and urinary disorders Azotaemia	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Renal and urinary disorders Haematuria	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Renal and urinary disorders Nephrolithiasis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Renal and urinary disorders Nephropathy toxic	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Renal and urinary disorders Renal failure	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/172 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Renal and urinary disorders Renal failure acute	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	2.9% 5/172 • Number of events 5 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	2.4% 4/167 • Number of events 4 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/169 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Renal and urinary disorders Renal failure chronic	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/167 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.8% 3/163 • Number of events 3 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Renal and urinary disorders Renal impairment	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Respiratory, thoracic and mediastinal disorders Choking	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.90% 2/221 • Number of events 3 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/163 • Number of events 4 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Skin and subcutaneous tissue disorders Stasis dermatitis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Skin and subcutaneous tissue disorders Diabetic foot	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Surgical and medical procedures Cardiac pacemaker insertion	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/169 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Surgical and medical procedures Cardiac pacemaker removal	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Surgical and medical procedures Cardioversion	0.90% 2/221 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Surgical and medical procedures Foot amputation	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Surgical and medical procedures Toe amputation	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Surgical and medical procedures Implantable defibrillator insertion	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/172 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Surgical and medical procedures Ventricular assist device insertion	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Surgical and medical procedures Cardiac rehabilitation therapy	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Surgical and medical procedures Cardiac resynchronisation therapy	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/172 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Surgical and medical procedures Cardiac ablation	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Surgical and medical procedures Tooth extraction	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Surgical and medical procedures Percutaneous coronary intervention	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Vascular disorders Aortic stenosis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Vascular disorders Circulatory collapse	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Vascular disorders Hypotension	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.58% 1/172 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.60% 1/167 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Vascular disorders Deep vein thrombosis	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.61% 1/163 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Vascular disorders Femoral artery occlusion	0.45% 1/221 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/169 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Vascular disorders Haemodynamic instability	0.00% 0/221 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/172 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/167 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.59% 1/169 • Number of events 1 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	0.00% 0/163 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.

Other adverse events

Other adverse events
Measure	Eplerenone (INSPRA®) n=221 participants at risk Eplerenone 25 milligram (mg) capsule every other day (EOD), on Day 1, Day 3, Day 5, etc, along with placebo capsule (matched to Eplerenone capsule) on Day 2, Day 4, Day 6, etc., and placebo tablet (matched to Finerenone tablet) once daily (OD).The dose could be increased to 25 mg OD at Day 30 and to 50 mg OD at Day 60 (or 25 mg OD if no up-titration occurred on Day 30) if both up-titration steps were performed. Treatment duration was for 90 days.	Finerenone(BAY94-8862) 2.5-5 mg OD n=172 participants at risk Finerenone 2.5 mg immediate-release (IR) tablets OD and placebo-matched to Eplerenone capsule OD, with possible up-titration to 5 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 5-10 mg OD n=163 participants at risk Finerenone 5 mg IR tablets OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 10 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 7.5-15 mg OD n=167 participants at risk Finerenone 7.5 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 15 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 10-20 mg OD n=169 participants at risk Finerenone 10 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.	Finerenone (BAY94-8862) 15-20 mg OD n=163 participants at risk Finerenone 15 mg IR tablet OD and placebo capsule (matched to Eplerenone capsule) OD, with possible up-titration to 20 mg OD at Day 30 (Day 30±2) and sham up-titration at Day 60 (Day 60±2). Treatment duration was for 90 days.
Cardiac disorders Cardiac failure	5.9% 13/221 • Number of events 14 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	8.1% 14/172 • Number of events 20 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	6.1% 10/163 • Number of events 11 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.0% 5/167 • Number of events 6 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.1% 7/169 • Number of events 7 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	6.1% 10/163 • Number of events 10 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Gastrointestinal disorders Diarrhoea	3.6% 8/221 • Number of events 8 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.5% 6/172 • Number of events 6 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.7% 6/163 • Number of events 6 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	6.0% 10/167 • Number of events 11 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.6% 6/169 • Number of events 6 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.3% 7/163 • Number of events 9 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Gastrointestinal disorders Nausea	3.2% 7/221 • Number of events 7 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	5.2% 9/172 • Number of events 12 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/163 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.0% 5/167 • Number of events 7 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.2% 2/169 • Number of events 2 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.7% 6/163 • Number of events 6 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Investigations Blood creatinine increased	5.4% 12/221 • Number of events 14 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	2.9% 5/172 • Number of events 5 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.3% 7/163 • Number of events 7 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.8% 3/167 • Number of events 3 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	2.4% 4/169 • Number of events 4 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.9% 8/163 • Number of events 9 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Metabolism and nutrition disorders Hyperkalaemia	3.6% 8/221 • Number of events 9 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	2.9% 5/172 • Number of events 5 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.3% 7/163 • Number of events 10 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.2% 7/167 • Number of events 7 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.6% 6/169 • Number of events 6 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	5.5% 9/163 • Number of events 9 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Metabolism and nutrition disorders Hypokalaemia	15.4% 34/221 • Number of events 44 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	11.6% 20/172 • Number of events 26 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	12.9% 21/163 • Number of events 28 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	9.0% 15/167 • Number of events 30 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	8.3% 14/169 • Number of events 18 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	10.4% 17/163 • Number of events 20 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Nervous system disorders Dizziness	5.4% 12/221 • Number of events 13 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.7% 8/172 • Number of events 8 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.7% 6/163 • Number of events 7 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.6% 6/167 • Number of events 6 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.1% 7/169 • Number of events 7 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.7% 6/163 • Number of events 7 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Renal and urinary disorders Renal impairment	3.6% 8/221 • Number of events 10 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.5% 6/172 • Number of events 8 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.3% 7/163 • Number of events 9 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.6% 6/167 • Number of events 10 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.7% 8/169 • Number of events 11 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	5.5% 9/163 • Number of events 9 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.0% 11/221 • Number of events 12 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	7.0% 12/172 • Number of events 13 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.3% 7/163 • Number of events 7 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	3.6% 6/167 • Number of events 7 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	1.8% 3/169 • Number of events 4 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	6.1% 10/163 • Number of events 11 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.
Vascular disorders Hypotension	5.0% 11/221 • Number of events 13 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.1% 7/172 • Number of events 7 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	6.7% 11/163 • Number of events 12 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	6.6% 11/167 • Number of events 14 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.1% 7/169 • Number of events 7 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.	4.9% 8/163 • Number of events 8 • Adverse events: from the start of study treatment until 3 days post-last dose, up to approximately 93 days. All Cause Mortality: assessed until 30 days post-last dose, up to approximately 120 days.

Additional Information

Therapeutic Area Head

Bayer HealthCare AG

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER