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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)

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ClinicalTrials.gov Identifier: NCT01951625
Recruitment Status : Completed
First Posted : September 26, 2013
Results First Posted : March 25, 2021
Last Update Posted : March 25, 2021
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Heart Failure
Interventions Drug: Vericiguat (BAY1021189) (1.25 mg)
Drug: Vericiguat (BAY1021189) (5 mg)
Drug: Placebo
Enrollment 456
Recruitment Details 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).
Pre-assignment Details 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.
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. 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. 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.
Period Title: Treatment Period
Started 92 91 91 91 91
Completed 73 70 76 69 74
Not Completed 19 21 15 22 17
Reason Not Completed
Protocol Violation             2             0             1             3             2
Physician Decision             0             0             0             0             1
Protocol driven decision point             0             5             0             2             1
Non compliance with study drug             1             2             2             0             0
Death             3             2             2             1             2
Adverse Event             7             10             9             8             8
Withdrawal by Subject             5             2             1             7             3
Lost to Follow-up             1             0             0             1             0
Period Title: Follow Up Period
Started 87 88 88 87 88
Completed 79 79 84 76 78
Not Completed 8 9 4 11 10
Reason Not Completed
Non-compliance with study drug             1             0             0             0             0
Death             1             3             2             2             1
Logistical difficulties             1             2             0             0             0
Adverse Event             0             3             2             3             5
Withdrawal by Subject             4             1             0             5             3
Lost to Follow-up             1             0             0             1             1
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg Total
Hide Arm/Group Description Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. 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. 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 of all reporting groups
Overall Number of Baseline Participants 92 91 91 91 91 456
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 92 participants 91 participants 91 participants 91 participants 91 participants 456 participants
67  (13.1) 67.6  (12.9) 67.6  (11.5) 66.7  (11.6) 68.9  (12.4) 67.6  (12.3)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 91 participants 91 participants 91 participants 91 participants 456 participants
<65
38
  41.3%
38
  41.8%
30
  33.0%
38
  41.8%
28
  30.8%
172
  37.7%
65-75
26
  28.3%
19
  20.9%
37
  40.7%
32
  35.2%
34
  37.4%
148
  32.5%
> 75
28
  30.4%
34
  37.4%
24
  26.4%
21
  23.1%
29
  31.9%
136
  29.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 91 participants 91 participants 91 participants 91 participants 456 participants
Female
19
  20.7%
21
  23.1%
19
  20.9%
17
  18.7%
14
  15.4%
90
  19.7%
Male
73
  79.3%
70
  76.9%
72
  79.1%
74
  81.3%
77
  84.6%
366
  80.3%
1.Primary Outcome
Title Change From Baseline in Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) to Week 12
Hide Description Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) is a circulating plasma biomarker of cardiovascular function and prognosis in heart failure.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS)
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg Pooled 2.5 mg up to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
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.
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.
The three highest dose arms (BAY1021189 2.5 mg, 2.5-5 mg, and 2.5-10 mg) were pooled.
Overall Number of Participants Analyzed 69 69 73 67 73 213
Mean (Standard Deviation)
Unit of Measure: log-transformed picograms per milliliter
-0.28  (0.8197) -0.265  (0.7658) -0.32  (0.7799) -0.353  (0.8404) -0.529  (0.9475) -0.402  (0.8603)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Pooled 2.5 mg up to 10 mg
Comments For the primary analysis, the three highest active treatment groups (BAY1021189 2.5mg, BAY1021189 2.5 to 5mg, BAY1021189 2.5 to 10mg) were pooled and compared to the assigned placebo treatment group with a one-sided two-sample t-test at the significance level of 5 percent (%). Results are reported including 90% confidence intervals (CI) for the difference of means. The difference between the pooled treatment group and the placebo group is difference of means on the log scale.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.1506
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Log-Scale mean difference
Estimated Value -0.122
Confidence Interval (2-Sided) 90%
-0.32 to 0.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, BAY1021189 From 2.5 to 10 mg
Comments In case of a significant result in the primary analysis of the primary endpoint, pairwise comparisons to Placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In case of non-significance of the primary analyses, these secondary analyses were specified as exploratory only, since the primary analyses were not significant.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0483
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Log-Scale mean difference
Estimated Value -0.2494
Confidence Interval (2-Sided) 90%
-0.5 to 0
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, BAY1021189 From 2.5 to 5 mg
Comments In case of a significant result in the primary analysis of the primary endpoint, pairwise comparisons to Placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In case of non-significance of the primary analyses, these secondary analyses were specified as exploratory only, since the primary analyses were not significant.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.3042
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Log-Scale mean difference
Estimated Value -0.0731
Confidence Interval (2-Sided) 90%
-0.31 to 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, BAY1021189 2.5 mg
Comments In case of a significant result in the primary analysis of the primary endpoint, pairwise comparisons to Placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In case of non-significance of the primary analyses, these secondary analyses were specified as exploratory only, since the primary analyses were not significant.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.3841
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Log-Scale mean difference
Estimated Value -0.0396
Confidence Interval (2-Sided) 90%
-0.26 to 0.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, BAY1021189 1.25 Milligram (mg)
Comments In case of a significant result in the primary analysis of the primary endpoint, pairwise comparisons to Placebo were performed in a hierarchical manner (from BAY1021189 from 2.5 to 10mg dose arm to BAY1021189 1.25mg dose arm). In case of non-significance of the primary analyses, these secondary analyses were specified as exploratory only.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.5444
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Log-Scale mean difference
Estimated Value 0.0151
Confidence Interval (2-Sided) 90%
-0.21 to 0.24
Estimation Comments [Not Specified]
2.Other Pre-specified Outcome
Title 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
Hide Description 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.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable subjects in full analysis set (FAS).
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
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.
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.
Overall Number of Participants Analyzed 92 91 91 91 91
Mean (Standard Deviation)
Unit of Measure: milliliter
Change in LVEDV Number Analyzed 70 participants 65 participants 69 participants 63 participants 70 participants
-7.259  (40.676) -5.525  (34.75) -9.632  (35.081) -17.093  (53.307) -7.324  (31.896)
Change in LVESV Number Analyzed 70 participants 65 participants 69 participants 63 participants 71 participants
-6.83  (32.407) -8.585  (27.385) -10.935  (27.146) -15.485  (43.191) -11.017  (26.525)
3.Other Pre-specified Outcome
Title Changes in Heart Function as Measured by Echocardiography, Left Ventricular Ejection Fraction (LVEF), From Baseline to Week 12
Hide Description 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.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable subjects in full analysis set (FAS).
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
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.
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.
Overall Number of Participants Analyzed 92 91 91 91 91
Mean (Standard Deviation)
Unit of Measure: percentage
1.515  (4.736) 2.84  (3.635) 2.741  (4.371) 2.07  (4.808) 3.682  (6.19)
4.Other Pre-specified Outcome
Title Change From Baseline in Systolic and Diastolic Blood Pressure to Week 12
Hide Description 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.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable subjects in safety analysis set (SAF).
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
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.
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.
Overall Number of Participants Analyzed 92 91 90 91 91
Mean (Standard Deviation)
Unit of Measure: millimeter of mercury (mmHg)
Change in SBP Number Analyzed 73 participants 70 participants 75 participants 69 participants 74 participants
-5.142  (12.829) -4.033  (13.3) -3.733  (16.509) -3.043  (15.934) -5.64  (15.509)
Change in DBP Number Analyzed 73 participants 70 participants 75 participants 69 participants 74 participants
-4.173  (8.6) -0.486  (9.298) -2.938  (11.101) -1.338  (9.528) -4.045  (10.604)
5.Other Pre-specified Outcome
Title Change From Baseline in Heart Rate to Week 12
Hide Description 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.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable subjects in safety analysis set (SAF).
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
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.
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.
Overall Number of Participants Analyzed 92 91 90 91 91
Mean (Standard Deviation)
Unit of Measure: Beats per minute
-0.562  (12.897) -0.352  (10.153) -1.556  (10.2) -0.99  (11.295) 0.545  (10.636)
6.Other Pre-specified Outcome
Title Number of Subjects With Clinical Events (Heart Failure [HF] Hospitalization and Cardio-Vascular [CV] Mortality)
Hide Description Clinical events (heart failure and mortality) were analyzed as CV death, and HF hospitalization at specified time points.
Time Frame Baseline until 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
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.
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.
Overall Number of Participants Analyzed 92 91 91 91 91
Measure Type: Count of Participants
Unit of Measure: Participants
HF hospitalizations
21
  22.8%
18
  19.8%
20
  22.0%
10
  11.0%
9
   9.9%
CV death
6
   6.5%
5
   5.5%
4
   4.4%
2
   2.2%
4
   4.4%
7.Other Pre-specified Outcome
Title Number of Subjects With Implantable Cardioverter Defibrillators Cardiac Resynchronization Therapy With Defibrillation (ICD/CRT-D) Therapy
Hide Description 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.
Time Frame Baseline upto 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
No analysis was performed for this end point.
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
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.
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.
Overall Number of Participants Analyzed 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Other Pre-specified Outcome
Title Number of Subjects With Treatment-Emergent Adverse Events
Hide Description 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.
Time Frame From the start of study treatment upto 5 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
SAF
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
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.
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.
Overall Number of Participants Analyzed 92 91 90 91 91
Measure Type: Count of Participants
Unit of Measure: Participants
66
  71.7%
60
  65.9%
62
  68.9%
62
  68.1%
56
  61.5%
9.Other Pre-specified Outcome
Title Change in Biomarkers From Baseline to Week 12: Osteopontin (ng/mL)
Hide Description [Not Specified]
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable subjects in FAS
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
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.
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.
Overall Number of Participants Analyzed 73 69 73 65 71
Mean (Standard Deviation)
Unit of Measure: nanogram(s)/milliliter (ng/mL)
2.79  (42.049) 3.812  (39.248) 3.266  (52.957) 8.485  (41.97) 3.709  (36.048)
10.Other Pre-specified Outcome
Title Change in Biomarkers From Baseline to Week 12: TIMP-4 (pg/mL)
Hide Description TIMP-4: tissue inhibitor of matrix metalloproteinases 4
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable subjects in FAS
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
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.
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.
Overall Number of Participants Analyzed 73 69 72 67 72
Mean (Standard Deviation)
Unit of Measure: picogram(s)/millilitre (pg/mL)
451.889  (1392.03) 1128.635  (1949.351) 643.626  (1441.954) 876.584  (1559.768) 397.603  (1420.223)
11.Other Pre-specified Outcome
Title Change in Biomarkers From Baseline to Week 12: cGMP (Pmol/mL)
Hide Description cGMP: cyclic guanosine monophosphate
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable subjects in FAS
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
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.
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.
Overall Number of Participants Analyzed 73 69 73 66 71
Mean (Standard Deviation)
Unit of Measure: picomole(s)/milliliter (pmol/mL)
78.874  (143.321) 79.767  (123.031) 92.352  (121.477) 80.888  (114.09) 63.563  (127.448)
12.Other Pre-specified Outcome
Title Change in Biomarkers From Baseline to Week 12: PIIINP (mcg/L)
Hide Description PIIINP: pro-collagen III N-terminal peptide
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable subjects in FAS
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
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.
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.
Overall Number of Participants Analyzed 70 69 72 67 73
Mean (Standard Deviation)
Unit of Measure: microgram(s)/liter (mcg/L)
-0.701  (7.246) 0.092  (3.958) 0.106  (5.145) -0.71  (3.774) -0.321  (4.452)
13.Other Pre-specified Outcome
Title Change in Biomarkers From Baseline to Week 12: GDF-15 (pg/mL)
Hide Description GDF-15: growth differentiation factor 15
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable subjects in FAS
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
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.
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.
Overall Number of Participants Analyzed 73 69 73 66 71
Mean (Standard Deviation)
Unit of Measure: pg/mL
429.432  (3212.229) 496.456  (3132.738) 285.472  (2837.237) 468.369  (1786.062) 244.63  (2906.763)
14.Other Pre-specified Outcome
Title Change in Biomarkers From Baseline to Week 12: ST2 (pg/mL)
Hide Description ST2: suppression of tumorigenicity 2
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable subjects in FAS
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
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.
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.
Overall Number of Participants Analyzed 73 69 72 67 72
Mean (Standard Deviation)
Unit of Measure: pg/mL
9457.677  (54702.45) 1623.869  (25086.72) -1217.77  (35166.41) 6933.941  (20747.71) 3681.668  (32293.77)
15.Other Pre-specified Outcome
Title Change in Biomarkers From Baseline to Week 12: Gal-3 (μg/mL)
Hide Description Gal-3: Galectin-3
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable subjects in FAS
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description:
Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
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.
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.
Overall Number of Participants Analyzed 72 68 73 64 71
Mean (Standard Deviation)
Unit of Measure: mcg/L
0.802  (13.818) 0.233  (6.208) -0.287  (3.729) 0.064  (5.64) -0.38  (4.551)
Time Frame Treatment-emergent AEs were collected after first application of study medication up to 5 calendar days after end of treatment with study medication.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Hide Arm/Group Description Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. Subjects received vericiguat (Verquvo, BAY1021189) 1.25 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28. 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. 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.
All-Cause Mortality
Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/92 (6.52%)      6/91 (6.59%)      5/90 (5.56%)      3/91 (3.30%)      4/91 (4.40%)    
Hide Serious Adverse Events
Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   30/92 (32.61%)      26/91 (28.57%)      26/90 (28.89%)      20/91 (21.98%)      25/91 (27.47%)    
Blood and lymphatic system disorders           
Anaemia * 1  1/92 (1.09%)  1 1/91 (1.10%)  1 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Thrombocytopenia * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Cardiac disorders           
Angina pectoris * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Atrial fibrillation * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 2/91 (2.20%)  2
Cardiac arrest * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Cardiac failure * 1  8/92 (8.70%)  14 13/91 (14.29%)  14 10/90 (11.11%)  11 3/91 (3.30%)  4 3/91 (3.30%)  4
Cardiac failure acute * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/91 (0.00%)  0
Cardiac failure chronic * 1  5/92 (5.43%)  5 2/91 (2.20%)  3 5/90 (5.56%)  5 3/91 (3.30%)  6 4/91 (4.40%)  4
Cardiac failure congestive * 1  1/92 (1.09%)  1 2/91 (2.20%)  3 3/90 (3.33%)  3 2/91 (2.20%)  2 3/91 (3.30%)  4
Ventricular fibrillation * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/91 (0.00%)  0
Ventricular tachycardia * 1  1/92 (1.09%)  1 1/91 (1.10%)  1 0/90 (0.00%)  0 1/91 (1.10%)  1 0/91 (0.00%)  0
Ischaemic cardiomyopathy * 1  0/92 (0.00%)  0 1/91 (1.10%)  1 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Left ventricular dysfunction * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/91 (0.00%)  0
Acute left ventricular failure * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/91 (0.00%)  0
Gastrointestinal disorders           
Abdominal pain * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Abdominal pain upper * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/91 (0.00%)  0
Diarrhoea * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Gastrointestinal haemorrhage * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/91 (0.00%)  0
Melaena * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Small intestinal obstruction * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/91 (0.00%)  0
Upper gastrointestinal haemorrhage * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/91 (0.00%)  0
Mechanical ileus * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Incarcerated umbilical hernia * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
General disorders           
Chest pain * 1  0/92 (0.00%)  0 1/91 (1.10%)  1 0/90 (0.00%)  0 1/91 (1.10%)  1 1/91 (1.10%)  1
Death * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/91 (0.00%)  0
Multi-organ failure * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/91 (0.00%)  0
Oedema peripheral * 1  0/92 (0.00%)  0 1/91 (1.10%)  1 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Sudden death * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 1/91 (1.10%)  1
General physical health deterioration * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Device dislocation * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/91 (0.00%)  0
Hepatobiliary disorders           
Cholangitis * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Cholecystitis * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Infections and infestations           
Bronchitis * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 2/91 (2.20%)  2
Escherichia sepsis * 1  0/92 (0.00%)  0 1/91 (1.10%)  1 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Pneumonia * 1  1/92 (1.09%)  1 1/91 (1.10%)  1 0/90 (0.00%)  0 2/91 (2.20%)  2 1/91 (1.10%)  1
Gastroenteritis * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/91 (0.00%)  0
Urinary tract infection * 1  0/92 (0.00%)  0 1/91 (1.10%)  1 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Pneumococcal sepsis * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/91 (0.00%)  0
Injury, poisoning and procedural complications           
Fall * 1  2/92 (2.17%)  2 2/91 (2.20%)  2 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Hip fracture * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Contusion * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Incision site haemorrhage * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  2
Investigations           
Transplant evaluation * 1  0/92 (0.00%)  0 1/91 (1.10%)  1 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Metabolism and nutrition disorders           
Fluid overload * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Gout * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Hyperglycaemia * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Hyperkalaemia * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Hypoglycaemia * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/91 (0.00%)  0
Hypokalaemia * 1  0/92 (0.00%)  0 1/91 (1.10%)  1 2/90 (2.22%)  2 0/91 (0.00%)  0 0/91 (0.00%)  0
Metabolic acidosis * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Type 2 diabetes mellitus * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/91 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Arthralgia * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/91 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Gastric cancer * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Intra-abdominal haemangioma * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/91 (0.00%)  0
Non-small cell lung cancer * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/91 (0.00%)  0
Nervous system disorders           
Cerebrovascular accident * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/91 (0.00%)  0
Cervicobrachial syndrome * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Subarachnoid haemorrhage * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/91 (0.00%)  0
Headache * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Syncope * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Renal and urinary disorders           
Renal failure * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/91 (0.00%)  0
Urinary retention * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 1/90 (1.11%)  1 0/91 (0.00%)  0 0/91 (0.00%)  0
Acute kidney injury * 1  3/92 (3.26%)  3 4/91 (4.40%)  4 2/90 (2.22%)  2 1/91 (1.10%)  1 3/91 (3.30%)  3
Respiratory, thoracic and mediastinal disorders           
Acute pulmonary oedema * 1  0/92 (0.00%)  0 1/91 (1.10%)  1 0/90 (0.00%)  0 1/91 (1.10%)  1 0/91 (0.00%)  0
Acute respiratory failure * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Chronic obstructive pulmonary disease * 1  0/92 (0.00%)  0 1/91 (1.10%)  1 1/90 (1.11%)  1 0/91 (0.00%)  0 0/91 (0.00%)  0
Dyspnoea * 1  0/92 (0.00%)  0 1/91 (1.10%)  1 0/90 (0.00%)  0 1/91 (1.10%)  1 1/91 (1.10%)  1
Pneumonia aspiration * 1  0/92 (0.00%)  0 1/91 (1.10%)  1 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Pulmonary congestion * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Pulmonary oedema * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 1/91 (1.10%)  1 0/91 (0.00%)  0
Skin and subcutaneous tissue disorders           
Rash * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Rash pruritic * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Surgical and medical procedures           
Catheter placement * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Vascular disorders           
Hypertension * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
Hypotension * 1  0/92 (0.00%)  0 0/91 (0.00%)  0 0/90 (0.00%)  0 0/91 (0.00%)  0 1/91 (1.10%)  1
Deep vein thrombosis * 1  0/92 (0.00%)  0 1/91 (1.10%)  1 0/90 (0.00%)  0 0/91 (0.00%)  0 0/91 (0.00%)  0
1
Term from vocabulary, MedDRA 18.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo BAY1021189 1.25 Milligram (mg) BAY1021189 2.5 mg BAY1021189 From 2.5 to 5 mg BAY1021189 From 2.5 to 10 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   24/92 (26.09%)      25/91 (27.47%)      20/90 (22.22%)      23/91 (25.27%)      28/91 (30.77%)    
Cardiac disorders           
Cardiac failure chronic * 1  4/92 (4.35%)  5 1/91 (1.10%)  1 5/90 (5.56%)  5 2/91 (2.20%)  2 0/91 (0.00%)  0
Gastrointestinal disorders           
Abdominal pain upper * 1  2/92 (2.17%)  2 5/91 (5.49%)  6 1/90 (1.11%)  1 1/91 (1.10%)  1 0/91 (0.00%)  0
Dyspepsia * 1  0/92 (0.00%)  0 1/91 (1.10%)  1 0/90 (0.00%)  0 1/91 (1.10%)  1 5/91 (5.49%)  7
Nausea * 1  3/92 (3.26%)  4 5/91 (5.49%)  6 3/90 (3.33%)  3 1/91 (1.10%)  1 1/91 (1.10%)  1
General disorders           
Asthenia * 1  3/92 (3.26%)  3 0/91 (0.00%)  0 2/90 (2.22%)  2 5/91 (5.49%)  5 2/91 (2.20%)  2
Metabolism and nutrition disorders           
Hyperuricaemia * 1  1/92 (1.09%)  1 0/91 (0.00%)  0 2/90 (2.22%)  2 5/91 (5.49%)  5 0/91 (0.00%)  0
Hypokalaemia * 1  3/92 (3.26%)  3 5/91 (5.49%)  5 2/90 (2.22%)  2 2/91 (2.20%)  2 5/91 (5.49%)  6
Nervous system disorders           
Dizziness * 1  5/92 (5.43%)  6 3/91 (3.30%)  3 2/90 (2.22%)  2 2/91 (2.20%)  2 5/91 (5.49%)  5
Respiratory, thoracic and mediastinal disorders           
Dyspnoea * 1  5/92 (5.43%)  5 1/91 (1.10%)  1 3/90 (3.33%)  3 2/91 (2.20%)  3 4/91 (4.40%)  4
Cough * 1  6/92 (6.52%)  7 8/91 (8.79%)  8 4/90 (4.44%)  4 4/91 (4.40%)  4 4/91 (4.40%)  4
Vascular disorders           
Hypotension * 1  6/92 (6.52%)  6 5/91 (5.49%)  5 5/90 (5.56%)  6 4/91 (4.40%)  4 14/91 (15.38%)  17
1
Term from vocabulary, MedDRA 18.0
*
Indicates events were collected by non-systematic assessment
Endpoints of "Change in 'health-related quality of life', 'Composite Congestion Score', 'NYHA function class', and 'background heart failure therapies' were assessed as exploratory. "Incidence of atrial fibrillation" is reported in AE summary.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head
Organization: Bayer AG
Phone: (+) 1-888-8422937
EMail: clinical-trials-contact@bayer.com
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01951625    
Other Study ID Numbers: 15371
2013-002287-11 ( EudraCT Number )
First Submitted: September 24, 2013
First Posted: September 26, 2013
Results First Submitted: January 20, 2021
Results First Posted: March 25, 2021
Last Update Posted: March 25, 2021