Trial Outcomes & Findings for Phase IIb Safety and Efficacy Study of Four Dose Regimens of BAY1021189 in Patients With Heart Failure With Reduced Ejection Fraction Suffering From Worsening Chronic Heart Failure (SOCRATES-REDUCED) (NCT NCT01951625)

NCT ID: NCT01951625

Last Updated: 2021-03-25

Results Overview

Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) is a circulating plasma biomarker of cardiovascular function and prognosis in heart failure.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 456 participants
• Primary outcome timeframe: Baseline, Week 12
• Results posted on: 2021-03-25

Participant Flow

The study was conducted at 144 centers in 24 countries between 29 November 2013 (first subject first visit) and 09 June 2015 (last subject last visit).

Overall 632 subjects were enrolled, of them 176 were screen failure and 456 were randomized. One subject did not receive study drug after randomization. Among the 455 subjects who received study drug 348 completed the study (that is completed both the treatment and follow-up periods) and 108 subjects did not complete the study.

Participant milestones

Measure	Placebo Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.
Treatment Period STARTED	92	91	91	91	91
Treatment Period COMPLETED	73	70	76	69	74
Treatment Period NOT COMPLETED	19	21	15	22	17
Follow Up Period STARTED	87	88	88	87	88
Follow Up Period COMPLETED	79	79	84	76	78
Follow Up Period NOT COMPLETED	8	9	4	11	10

Reasons for withdrawal

Measure	Placebo Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.
Treatment Period Protocol Violation	2	0	1	3	2
Treatment Period Physician Decision	0	0	0	0	1
Treatment Period Protocol driven decision point	0	5	0	2	1
Treatment Period Non compliance with study drug	1	2	2	0	0
Treatment Period Death	3	2	2	1	2
Treatment Period Adverse Event	7	10	9	8	8
Treatment Period Withdrawal by Subject	5	2	1	7	3
Treatment Period Lost to Follow-up	1	0	0	1	0
Follow Up Period Non-compliance with study drug	1	0	0	0	0
Follow Up Period Death	1	3	2	2	1
Follow Up Period Logistical difficulties	1	2	0	0	0
Follow Up Period Adverse Event	0	3	2	3	5
Follow Up Period Withdrawal by Subject	4	1	0	5	3
Follow Up Period Lost to Follow-up	1	0	0	1	1

Baseline Characteristics

Phase IIb Safety and Efficacy Study of Four Dose Regimens of BAY1021189 in Patients With Heart Failure With Reduced Ejection Fraction Suffering From Worsening Chronic Heart Failure (SOCRATES-REDUCED)

Baseline characteristics by cohort

Measure	Placebo n=92 Participants Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.	Total n=456 Participants Total of all reporting groups
Age, Continuous	67 years STANDARD_DEVIATION 13.1 • n=5 Participants	67.6 years STANDARD_DEVIATION 12.9 • n=7 Participants	67.6 years STANDARD_DEVIATION 11.5 • n=5 Participants	66.7 years STANDARD_DEVIATION 11.6 • n=4 Participants	68.9 years STANDARD_DEVIATION 12.4 • n=21 Participants	67.6 years STANDARD_DEVIATION 12.3 • n=8 Participants
Age, Customized <65	38 Participants n=5 Participants	38 Participants n=7 Participants	30 Participants n=5 Participants	38 Participants n=4 Participants	28 Participants n=21 Participants	172 Participants n=8 Participants
Age, Customized 65-75	26 Participants n=5 Participants	19 Participants n=7 Participants	37 Participants n=5 Participants	32 Participants n=4 Participants	34 Participants n=21 Participants	148 Participants n=8 Participants
Age, Customized > 75	28 Participants n=5 Participants	34 Participants n=7 Participants	24 Participants n=5 Participants	21 Participants n=4 Participants	29 Participants n=21 Participants	136 Participants n=8 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	21 Participants n=7 Participants	19 Participants n=5 Participants	17 Participants n=4 Participants	14 Participants n=21 Participants	90 Participants n=8 Participants
Sex: Female, Male Male	73 Participants n=5 Participants	70 Participants n=7 Participants	72 Participants n=5 Participants	74 Participants n=4 Participants	77 Participants n=21 Participants	366 Participants n=8 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: Per Protocol Set (PPS)

Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) is a circulating plasma biomarker of cardiovascular function and prognosis in heart failure.

Outcome measures

Measure	Placebo n=69 Participants Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=69 Participants Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=73 Participants Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=67 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=73 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.	Pooled 2.5 mg up to 10 mg n=213 Participants The three highest dose arms (BAY1021189 2.5 mg, 2.5-5 mg, and 2.5-10 mg) were pooled.
Change From Baseline in Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) to Week 12	-0.28 log-transformed picograms per milliliter Standard Deviation 0.8197	-0.265 log-transformed picograms per milliliter Standard Deviation 0.7658	-0.32 log-transformed picograms per milliliter Standard Deviation 0.7799	-0.353 log-transformed picograms per milliliter Standard Deviation 0.8404	-0.529 log-transformed picograms per milliliter Standard Deviation 0.9475	-0.402 log-transformed picograms per milliliter Standard Deviation 0.8603

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 12

Population: Evaluable subjects in full analysis set (FAS).

Left Ventricular End-Diastolic Volume (LVEDV) and Left ventricular end-systolic volume (LVESV) are measured echocardiography parameter. These are acquired during a non-invasive echocardiography examination.

Outcome measures

Measure	Placebo n=92 Participants Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.	Pooled 2.5 mg up to 10 mg The three highest dose arms (BAY1021189 2.5 mg, 2.5-5 mg, and 2.5-10 mg) were pooled.
Changes in Heart Function as Measured by Echocardiography, Left Ventricular End-Diastolic Volume (LVEDV), and Left Ventricular End-Systolic Volume (LVESV) From Baseline to Week 12 Change in LVEDV	-7.259 milliliter Standard Deviation 40.676	-5.525 milliliter Standard Deviation 34.75	-9.632 milliliter Standard Deviation 35.081	-17.093 milliliter Standard Deviation 53.307	-7.324 milliliter Standard Deviation 31.896	—
Changes in Heart Function as Measured by Echocardiography, Left Ventricular End-Diastolic Volume (LVEDV), and Left Ventricular End-Systolic Volume (LVESV) From Baseline to Week 12 Change in LVESV	-6.83 milliliter Standard Deviation 32.407	-8.585 milliliter Standard Deviation 27.385	-10.935 milliliter Standard Deviation 27.146	-15.485 milliliter Standard Deviation 43.191	-11.017 milliliter Standard Deviation 26.525	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 12

Population: Evaluable subjects in full analysis set (FAS).

The left ventricular ejection fraction work index (LVEF) is a calculated echocardiography parameter. LVEF is derived from the directly measured parameters left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). These 2 parameters are acquired during a noninvasive echocardiography examination. Formula: LVEF = 100*(LVEDV - LVESV)/LVEDV.

Outcome measures

Measure	Placebo n=92 Participants Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.	Pooled 2.5 mg up to 10 mg The three highest dose arms (BAY1021189 2.5 mg, 2.5-5 mg, and 2.5-10 mg) were pooled.
Changes in Heart Function as Measured by Echocardiography, Left Ventricular Ejection Fraction (LVEF), From Baseline to Week 12	1.515 percentage Standard Deviation 4.736	2.84 percentage Standard Deviation 3.635	2.741 percentage Standard Deviation 4.371	2.07 percentage Standard Deviation 4.808	3.682 percentage Standard Deviation 6.19	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 12

Population: Evaluable subjects in safety analysis set (SAF).

Blood pressure was measured by monitor measurements after 10 minutes resting in a supine position (3 measurements taken approximately 2 minutes apart).The changes in blood pressure were recorded and the mean of the three measurements was analyzed.

Outcome measures

Measure	Placebo n=92 Participants Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=90 Participants Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.	Pooled 2.5 mg up to 10 mg The three highest dose arms (BAY1021189 2.5 mg, 2.5-5 mg, and 2.5-10 mg) were pooled.
Change From Baseline in Systolic and Diastolic Blood Pressure to Week 12 Change in SBP	-5.142 millimeter of mercury (mmHg) Standard Deviation 12.829	-4.033 millimeter of mercury (mmHg) Standard Deviation 13.3	-3.733 millimeter of mercury (mmHg) Standard Deviation 16.509	-3.043 millimeter of mercury (mmHg) Standard Deviation 15.934	-5.64 millimeter of mercury (mmHg) Standard Deviation 15.509	—
Change From Baseline in Systolic and Diastolic Blood Pressure to Week 12 Change in DBP	-4.173 millimeter of mercury (mmHg) Standard Deviation 8.6	-0.486 millimeter of mercury (mmHg) Standard Deviation 9.298	-2.938 millimeter of mercury (mmHg) Standard Deviation 11.101	-1.338 millimeter of mercury (mmHg) Standard Deviation 9.528	-4.045 millimeter of mercury (mmHg) Standard Deviation 10.604	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 12

Population: Evaluable subjects in safety analysis set (SAF).

Heart rate was measured after 10 minutes resting in a supine position (3 measurements taken approximately 2 minutes apart). The changes in heart rate were recorded and the mean of the three measurements was analyzed.

Outcome measures

Measure	Placebo n=92 Participants Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=90 Participants Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.	Pooled 2.5 mg up to 10 mg The three highest dose arms (BAY1021189 2.5 mg, 2.5-5 mg, and 2.5-10 mg) were pooled.
Change From Baseline in Heart Rate to Week 12	-0.562 Beats per minute Standard Deviation 12.897	-0.352 Beats per minute Standard Deviation 10.153	-1.556 Beats per minute Standard Deviation 10.2	-0.99 Beats per minute Standard Deviation 11.295	0.545 Beats per minute Standard Deviation 10.636	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline until 16 weeks

Population: FAS

Clinical events (heart failure and mortality) were analyzed as CV death, and HF hospitalization at specified time points.

Outcome measures

Measure	Placebo n=92 Participants Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.	Pooled 2.5 mg up to 10 mg The three highest dose arms (BAY1021189 2.5 mg, 2.5-5 mg, and 2.5-10 mg) were pooled.
Number of Subjects With Clinical Events (Heart Failure [HF] Hospitalization and Cardio-Vascular [CV] Mortality) HF hospitalizations	21 Participants	18 Participants	20 Participants	10 Participants	9 Participants	—
Number of Subjects With Clinical Events (Heart Failure [HF] Hospitalization and Cardio-Vascular [CV] Mortality) CV death	6 Participants	5 Participants	4 Participants	2 Participants	4 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline upto 16 weeks

Population: No analysis was performed for this end point.

ICD / CRT with defibrillation therapy (CRT-D) included previous appropriate interventions such as shocks or anti-tachycardic pacing (ATP) when diagnostic of sustained ventricular tachycardias in pre defined rapid zone.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From the start of study treatment upto 5 days after the last dose of study drug

Population: SAF

An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; and another medically important serious event as judged by the investigator. AEs are considered to be treatment-emergent if they have started or worsened after first application of study drug up to 5 days after end of treatment with study drug.

Outcome measures

Measure	Placebo n=92 Participants Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=90 Participants Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=91 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.	Pooled 2.5 mg up to 10 mg The three highest dose arms (BAY1021189 2.5 mg, 2.5-5 mg, and 2.5-10 mg) were pooled.
Number of Subjects With Treatment-Emergent Adverse Events	66 Participants	60 Participants	62 Participants	62 Participants	56 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 12

Population: Evaluable subjects in FAS

Outcome measures

Measure	Placebo n=73 Participants Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=69 Participants Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=73 Participants Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=65 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=71 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.	Pooled 2.5 mg up to 10 mg The three highest dose arms (BAY1021189 2.5 mg, 2.5-5 mg, and 2.5-10 mg) were pooled.
Change in Biomarkers From Baseline to Week 12: Osteopontin (ng/mL)	2.79 nanogram(s)/milliliter (ng/mL) Standard Deviation 42.049 • Interval 42.049 to	3.812 nanogram(s)/milliliter (ng/mL) Standard Deviation 39.248 • Interval 39.248 to	3.266 nanogram(s)/milliliter (ng/mL) Standard Deviation 52.957 • Interval 52.957 to	8.485 nanogram(s)/milliliter (ng/mL) Standard Deviation 41.97 • Interval 41.97 to	3.709 nanogram(s)/milliliter (ng/mL) Standard Deviation 36.048 • Interval 36.048 to	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 12

Population: Evaluable subjects in FAS

TIMP-4: tissue inhibitor of matrix metalloproteinases 4

Outcome measures

Measure	Placebo n=73 Participants Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=69 Participants Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=72 Participants Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=67 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=72 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.	Pooled 2.5 mg up to 10 mg The three highest dose arms (BAY1021189 2.5 mg, 2.5-5 mg, and 2.5-10 mg) were pooled.
Change in Biomarkers From Baseline to Week 12: TIMP-4 (pg/mL)	451.889 picogram(s)/millilitre (pg/mL) Standard Deviation 1392.03 • Interval 1392.03 to	1128.635 picogram(s)/millilitre (pg/mL) Standard Deviation 1949.351 • Interval 1949.351 to	643.626 picogram(s)/millilitre (pg/mL) Standard Deviation 1441.954 • Interval 1441.954 to	876.584 picogram(s)/millilitre (pg/mL) Standard Deviation 1559.768 • Interval 1559.768 to	397.603 picogram(s)/millilitre (pg/mL) Standard Deviation 1420.223 • Interval 1420.223 to	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 12

Population: Evaluable subjects in FAS

cGMP: cyclic guanosine monophosphate

Outcome measures

Measure	Placebo n=73 Participants Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=69 Participants Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=73 Participants Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=66 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=71 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.	Pooled 2.5 mg up to 10 mg The three highest dose arms (BAY1021189 2.5 mg, 2.5-5 mg, and 2.5-10 mg) were pooled.
Change in Biomarkers From Baseline to Week 12: cGMP (Pmol/mL)	78.874 picomole(s)/milliliter (pmol/mL) Standard Deviation 143.321 • Interval 143.321 to	79.767 picomole(s)/milliliter (pmol/mL) Standard Deviation 123.031 • Interval 123.031 to	92.352 picomole(s)/milliliter (pmol/mL) Standard Deviation 121.477 • Interval 121.477 to	80.888 picomole(s)/milliliter (pmol/mL) Standard Deviation 114.09 • Interval 114.09 to	63.563 picomole(s)/milliliter (pmol/mL) Standard Deviation 127.448 • Interval 127.448 to	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 12

Population: Evaluable subjects in FAS

PIIINP: pro-collagen III N-terminal peptide

Outcome measures

Measure	Placebo n=70 Participants Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=69 Participants Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=72 Participants Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=67 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=73 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.	Pooled 2.5 mg up to 10 mg The three highest dose arms (BAY1021189 2.5 mg, 2.5-5 mg, and 2.5-10 mg) were pooled.
Change in Biomarkers From Baseline to Week 12: PIIINP (mcg/L)	-0.701 microgram(s)/liter (mcg/L) Standard Deviation 7.246 • Interval 7.246 to	0.092 microgram(s)/liter (mcg/L) Standard Deviation 3.958 • Interval 3.958 to	0.106 microgram(s)/liter (mcg/L) Standard Deviation 5.145 • Interval 5.145 to	-0.71 microgram(s)/liter (mcg/L) Standard Deviation 3.774 • Interval 3.774 to	-0.321 microgram(s)/liter (mcg/L) Standard Deviation 4.452 • Interval 4.452 to	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 12

Population: Evaluable subjects in FAS

GDF-15: growth differentiation factor 15

Outcome measures

Measure	Placebo n=73 Participants Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=69 Participants Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=73 Participants Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=66 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=71 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.	Pooled 2.5 mg up to 10 mg The three highest dose arms (BAY1021189 2.5 mg, 2.5-5 mg, and 2.5-10 mg) were pooled.
Change in Biomarkers From Baseline to Week 12: GDF-15 (pg/mL)	429.432 pg/mL Standard Deviation 3212.229 • Interval 3212.229 to	496.456 pg/mL Standard Deviation 3132.738 • Interval 3132.738 to	285.472 pg/mL Standard Deviation 2837.237 • Interval 2837.237 to	468.369 pg/mL Standard Deviation 1786.062 • Interval 1786.062 to	244.63 pg/mL Standard Deviation 2906.763 • Interval 2906.763 to	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 12

Population: Evaluable subjects in FAS

ST2: suppression of tumorigenicity 2

Outcome measures

Measure	Placebo n=73 Participants Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=69 Participants Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=72 Participants Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=67 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=72 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.	Pooled 2.5 mg up to 10 mg The three highest dose arms (BAY1021189 2.5 mg, 2.5-5 mg, and 2.5-10 mg) were pooled.
Change in Biomarkers From Baseline to Week 12: ST2 (pg/mL)	9457.677 pg/mL Standard Deviation 54702.45 • Interval 54702.45 to	1623.869 pg/mL Standard Deviation 25086.72 • Interval 25086.72 to	-1217.77 pg/mL Standard Deviation 35166.41 • Interval 35166.41 to	6933.941 pg/mL Standard Deviation 20747.71 • Interval 20747.71 to	3681.668 pg/mL Standard Deviation 32293.77 • Interval 32293.77 to	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 12

Population: Evaluable subjects in FAS

Gal-3: Galectin-3

Outcome measures

Measure	Placebo n=72 Participants Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=68 Participants Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=73 Participants Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=64 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=71 Participants Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.	Pooled 2.5 mg up to 10 mg The three highest dose arms (BAY1021189 2.5 mg, 2.5-5 mg, and 2.5-10 mg) were pooled.
Change in Biomarkers From Baseline to Week 12: Gal-3 (μg/mL)	0.802 mcg/L Standard Deviation 13.818 • Interval 13.818 to	0.233 mcg/L Standard Deviation 6.208 • Interval 6.208 to	-0.287 mcg/L Standard Deviation 3.729 • Interval 3.729 to	0.064 mcg/L Standard Deviation 5.64 • Interval 5.64 to	-0.38 mcg/L Standard Deviation 4.551 • Interval 4.551 to	—

Adverse Events

Placebo

Serious events: 30 serious events

Other events: 24 other events

Deaths: 6 deaths

BAY1021189 1.25 Milligram (mg)

Serious events: 26 serious events

Other events: 25 other events

Deaths: 6 deaths

BAY1021189 2.5 mg

Serious events: 26 serious events

Other events: 20 other events

Deaths: 5 deaths

BAY1021189 From 2.5 to 5 mg

Serious events: 20 serious events

Other events: 23 other events

Deaths: 3 deaths

BAY1021189 From 2.5 to 10 mg

Serious events: 25 serious events

Other events: 28 other events

Deaths: 4 deaths

Serious adverse events

Measure	Placebo n=92 participants at risk Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=91 participants at risk Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=90 participants at risk Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=91 participants at risk Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=91 participants at risk Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Blood and lymphatic system disorders Anaemia	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Blood and lymphatic system disorders Thrombocytopenia	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Cardiac disorders Angina pectoris	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Cardiac disorders Atrial fibrillation	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/91 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Cardiac disorders Cardiac arrest	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Cardiac disorders Cardiac failure	8.7% 8/92 • Number of events 14 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	14.3% 13/91 • Number of events 14 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	11.1% 10/90 • Number of events 11 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	3.3% 3/91 • Number of events 4 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	3.3% 3/91 • Number of events 4 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Cardiac disorders Cardiac failure acute	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Cardiac disorders Cardiac failure chronic	5.4% 5/92 • Number of events 5 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/91 • Number of events 3 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	5.6% 5/90 • Number of events 5 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	3.3% 3/91 • Number of events 6 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	4.4% 4/91 • Number of events 4 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Cardiac disorders Cardiac failure congestive	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/91 • Number of events 3 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	3.3% 3/90 • Number of events 3 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/91 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	3.3% 3/91 • Number of events 4 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Cardiac disorders Ventricular fibrillation	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Cardiac disorders Ventricular tachycardia	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Cardiac disorders Ischaemic cardiomyopathy	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Cardiac disorders Left ventricular dysfunction	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/90 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Cardiac disorders Acute left ventricular failure	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Gastrointestinal disorders Abdominal pain	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/90 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Gastrointestinal disorders Diarrhoea	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Gastrointestinal disorders Melaena	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/90 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Gastrointestinal disorders Mechanical ileus	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Gastrointestinal disorders Incarcerated umbilical hernia	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
General disorders Chest pain	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
General disorders Death	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/90 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
General disorders Multi-organ failure	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
General disorders Oedema peripheral	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
General disorders Sudden death	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
General disorders General physical health deterioration	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
General disorders Device dislocation	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Hepatobiliary disorders Cholangitis	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Hepatobiliary disorders Cholecystitis	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Infections and infestations Bronchitis	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/91 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Infections and infestations Escherichia sepsis	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Infections and infestations Pneumonia	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/91 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Infections and infestations Gastroenteritis	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/90 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Infections and infestations Urinary tract infection	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Infections and infestations Pneumococcal sepsis	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/90 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Injury, poisoning and procedural complications Fall	2.2% 2/92 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/91 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Injury, poisoning and procedural complications Contusion	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Injury, poisoning and procedural complications Incision site haemorrhage	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Metabolism and nutrition disorders Fluid overload	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Investigations Transplant evaluation	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Metabolism and nutrition disorders Gout	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Metabolism and nutrition disorders Hyperglycaemia	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Metabolism and nutrition disorders Hyperkalaemia	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/90 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/90 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Metabolism and nutrition disorders Metabolic acidosis	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/90 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intra-abdominal haemangioma	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/90 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Nervous system disorders Cerebrovascular accident	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/90 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Nervous system disorders Cervicobrachial syndrome	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/90 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Nervous system disorders Headache	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Nervous system disorders Syncope	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Renal and urinary disorders Renal failure	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/90 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Renal and urinary disorders Urinary retention	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/90 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Renal and urinary disorders Acute kidney injury	3.3% 3/92 • Number of events 3 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	4.4% 4/91 • Number of events 4 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/90 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	3.3% 3/91 • Number of events 3 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/90 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Skin and subcutaneous tissue disorders Rash	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Surgical and medical procedures Catheter placement	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Vascular disorders Hypertension	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Vascular disorders Hypotension	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Vascular disorders Deep vein thrombosis	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.

Other adverse events

Measure	Placebo n=92 participants at risk Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 1.25 Milligram (mg) n=91 participants at risk Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 2.5 mg n=90 participants at risk Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	BAY1021189 From 2.5 to 5 mg n=91 participants at risk Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	BAY1021189 From 2.5 to 10 mg n=91 participants at risk Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.
Cardiac disorders Cardiac failure chronic	4.3% 4/92 • Number of events 5 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	5.6% 5/90 • Number of events 5 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/91 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Gastrointestinal disorders Abdominal pain upper	2.2% 2/92 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	5.5% 5/91 • Number of events 6 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/90 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Gastrointestinal disorders Dyspepsia	0.00% 0/92 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/90 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	5.5% 5/91 • Number of events 7 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Gastrointestinal disorders Nausea	3.3% 3/92 • Number of events 4 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	5.5% 5/91 • Number of events 6 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	3.3% 3/90 • Number of events 3 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
General disorders Asthenia	3.3% 3/92 • Number of events 3 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/90 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	5.5% 5/91 • Number of events 5 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/91 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Metabolism and nutrition disorders Hyperuricaemia	1.1% 1/92 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/90 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	5.5% 5/91 • Number of events 5 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	0.00% 0/91 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Metabolism and nutrition disorders Hypokalaemia	3.3% 3/92 • Number of events 3 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	5.5% 5/91 • Number of events 5 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/90 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/91 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	5.5% 5/91 • Number of events 6 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Nervous system disorders Dizziness	5.4% 5/92 • Number of events 6 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	3.3% 3/91 • Number of events 3 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/90 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/91 • Number of events 2 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	5.5% 5/91 • Number of events 5 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.4% 5/92 • Number of events 5 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	1.1% 1/91 • Number of events 1 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	3.3% 3/90 • Number of events 3 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	2.2% 2/91 • Number of events 3 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	4.4% 4/91 • Number of events 4 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Respiratory, thoracic and mediastinal disorders Cough	6.5% 6/92 • Number of events 7 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	8.8% 8/91 • Number of events 8 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	4.4% 4/90 • Number of events 4 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	4.4% 4/91 • Number of events 4 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	4.4% 4/91 • Number of events 4 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Vascular disorders Hypotension	6.5% 6/92 • Number of events 6 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	5.5% 5/91 • Number of events 5 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	5.6% 5/90 • Number of events 6 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	4.4% 4/91 • Number of events 4 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.	15.4% 14/91 • Number of events 17 • Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.

Additional Information

Therapeutic Area Head

Bayer AG

Phone: (+) 1-888-8422937

Email: clinical-trials-contact@bayer.com

Results disclosure agreements

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