Phase IIb Safety and Efficacy Study of Four Dose Regimens... | NCT01951625

NCT01951625

ID	Type	Description	Link
2013-002287-11	EudraCT Number

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Vericiguat (BAY1021189) (10 mg)	Experimental	2.5 mg orally once daily for 2 weeks, up-titration to 5 mg orally once daily for 2 weeks, up-titration to 10 mg orally once daily for 8 weeks	Drug: Vericiguat (BAY1021189) (1.25 mg) Drug: Vericiguat (BAY1021189) (5 mg)
Vericiguat (BAY1021189) (5 mg)	Experimental	2.5 mg orally once daily for 2 weeks, then 5 mg orally once daily for 10 weeks (with sham titration)	Drug: Vericiguat (BAY1021189) (1.25 mg) Drug: Vericiguat (BAY1021189) (5 mg)
Vericiguat (BAY1021189) (2.5 mg)	Experimental	2.5 mg orally once daily for 12 weeks (with sham titrations)	Drug: Vericiguat (BAY1021189) (1.25 mg)
Vericiguat (BAY1021189) (1.25 mg)	Experimental	1.25 mg orally once daily for 12 weeks (with sham titrations)	Drug: Vericiguat (BAY1021189) (1.25 mg)
Placebo	Placebo Comparator	Orally once daily for 12 weeks (with sham titrations)	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Vericiguat (BAY1021189) (1.25 mg)	Drug	1.25 mg BAY1021189 tablets	Vericiguat (BAY1021189) (1.25 mg) Vericiguat (BAY1021189) (10 mg) Vericiguat (BAY1021189) (2.5 mg)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) to Week 12	Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) is a circulating plasma biomarker of cardiovascular function and prognosis in heart failure.	Baseline, Week 12

Other Outcomes

Measure	Description	Time Frame
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	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.	Baseline, Week 12

Eligibility Module

Name	Affiliation	Role
Bayer Study Director	Bayer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Fountain Valley	California	92708	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
25056511	Result	Pieske B, Butler J, Filippatos G, Lam C, Maggioni AP, Ponikowski P, Shah S, Solomon S, Kraigher-Krainer E, Samano ET, Scalise AV, Muller K, Roessig L, Gheorghiade M; SOCRATES Investigators and Coordinators. Rationale and design of the SOluble guanylate Cyclase stimulatoR in heArT failurE Studies (SOCRATES). Eur J Heart Fail. 2014 Sep;16(9):1026-38. doi: 10.1002/ejhf.135. Epub 2014 Jul 24.
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Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
FG001	BAY1021189 1.25 Milligram (mg)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
BG001	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.
BG002	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.
BG003	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.
BG004	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.
BG005	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00067± 13.1 BG00167.6± 12.9 BG00267.6± 11.5 BG003

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<65	BG00038 BG00138 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00019 BG00121 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) to Week 12

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

Per Protocol Set (PPS)

Posted

Mean

Standard Deviation

log-transformed picograms per milliliter

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	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.
OG002	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.
OG003	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.
OG004	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.
OG005	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.

Units	Counts
Participants	OG00069 OG00169 OG00273 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.28± 0.8197 OG001-0.265± 0.7658 OG002-0.32± 0.7799 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG005	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.	t-test, 1 sided		= 0.1506		Log-Scale mean difference	-0.122			2-Sided	90	-0.32	0.07					Other

Other Pre-specified

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

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.

Evaluable subjects in full analysis set (FAS).

Posted

Mean

Standard Deviation

milliliter

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	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.
OG002	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.
OG003	BAY1021189 From 2.5 to 5 mg

Other Pre-specified

Changes in Heart Function as Measured by Echocardiography, Left Ventricular Ejection Fraction (LVEF), From Baseline to Week 12

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.

Evaluable subjects in full analysis set (FAS).

Posted

Mean

Standard Deviation

percentage

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	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.
OG002	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.

Other Pre-specified

Change From Baseline in Systolic and Diastolic Blood Pressure to Week 12

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.

Evaluable subjects in safety analysis set (SAF).

Posted

Mean

Standard Deviation

millimeter of mercury (mmHg)

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	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.
OG002	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.
OG003	BAY1021189 From 2.5 to 5 mg

Other Pre-specified

Change From Baseline in Heart Rate to Week 12

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.

Evaluable subjects in safety analysis set (SAF).

Posted

Mean

Standard Deviation

Beats per minute

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	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.
OG002	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.
OG003	BAY1021189 From 2.5 to 5 mg

Other Pre-specified

Number of Subjects With Clinical Events (Heart Failure [HF] Hospitalization and Cardio-Vascular [CV] Mortality)

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

FAS

Posted

Count of Participants

Participants

Baseline until 16 weeks

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	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.
OG002	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.
OG003	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.

Other Pre-specified

Number of Subjects With Implantable Cardioverter Defibrillators Cardiac Resynchronization Therapy With Defibrillation (ICD/CRT-D) Therapy

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.

No analysis was performed for this end point.

Posted

Baseline upto 16 weeks

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	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.
OG002	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.
OG003	BAY1021189 From 2.5 to 5 mg

Other Pre-specified

Number of Subjects With Treatment-Emergent Adverse Events

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.

SAF

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	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.
OG002	BAY1021189 2.5 mg

Other Pre-specified

Change in Biomarkers From Baseline to Week 12: Osteopontin (ng/mL)

Evaluable subjects in FAS

Posted

Mean

Standard Deviation

nanogram(s)/milliliter (ng/mL)

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	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.
OG002	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.
OG003	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.

Other Pre-specified

Change in Biomarkers From Baseline to Week 12: TIMP-4 (pg/mL)

TIMP-4: tissue inhibitor of matrix metalloproteinases 4

Evaluable subjects in FAS

Posted

Mean

Standard Deviation

picogram(s)/millilitre (pg/mL)

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	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.
OG002	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.
OG003	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.

Other Pre-specified

Change in Biomarkers From Baseline to Week 12: cGMP (Pmol/mL)

cGMP: cyclic guanosine monophosphate

Evaluable subjects in FAS

Posted

Mean

Standard Deviation

picomole(s)/milliliter (pmol/mL)

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	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.
OG002	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.
OG003	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.

Other Pre-specified

Change in Biomarkers From Baseline to Week 12: PIIINP (mcg/L)

PIIINP: pro-collagen III N-terminal peptide

Evaluable subjects in FAS

Posted

Mean

Standard Deviation

microgram(s)/liter (mcg/L)

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	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.
OG002	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.
OG003	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.

Other Pre-specified

Change in Biomarkers From Baseline to Week 12: GDF-15 (pg/mL)

GDF-15: growth differentiation factor 15

Evaluable subjects in FAS

Posted

Mean

Standard Deviation

pg/mL

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	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.
OG002	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.
OG003	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.

Other Pre-specified

Change in Biomarkers From Baseline to Week 12: ST2 (pg/mL)

ST2: suppression of tumorigenicity 2

Evaluable subjects in FAS

Posted

Mean

Standard Deviation

pg/mL

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	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.
OG002	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.
OG003	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.

Other Pre-specified

Change in Biomarkers From Baseline to Week 12: Gal-3 (μg/mL)

Gal-3: Galectin-3

Evaluable subjects in FAS

Posted

Mean

Standard Deviation

mcg/L

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	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.
OG002	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.
OG003	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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Subjects received placebo matched to vericiguat (Verquvo, BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	6	92	30	92	24	92
EG001	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.	6	91	26	91	25	91
EG002	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.	5	90	26	90	20	90
EG003	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.	3	91	20	91	23	91
EG004	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.	4	91	25	91	28	91

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected91 at risk EG0020 events0 affected90 at risk EG0030 events0 affected91 at risk EG0041 events1 affected91 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG00014 events8 affected92 at risk EG00114 events13 affected91 at risk EG00211 events10 affected90 at risk EG003
Cardiac failure acute	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Cardiac failure chronic	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0005 events5 affected92 at risk EG0013 events2 affected91 at risk EG0025 events5 affected90 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0013 events2 affected91 at risk EG0023 events3 affected90 at risk EG003
Ventricular fibrillation	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Ventricular tachycardia	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected91 at risk EG0020 events0 affected90 at risk EG003
Ischaemic cardiomyopathy	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected91 at risk EG0020 events0 affected90 at risk EG003
Left ventricular dysfunction	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0021 events1 affected90 at risk EG003
Acute left ventricular failure	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0021 events1 affected90 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Melaena	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0021 events1 affected90 at risk EG003
Mechanical ileus	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Incarcerated umbilical hernia	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Chest pain	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected91 at risk EG0020 events0 affected90 at risk EG003
Death	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0021 events1 affected90 at risk EG003
Multi-organ failure	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Oedema peripheral	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected91 at risk EG0020 events0 affected90 at risk EG003
Sudden death	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
General physical health deterioration	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Device dislocation	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Bronchitis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Escherichia sepsis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected91 at risk EG0020 events0 affected90 at risk EG003
Pneumonia	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected91 at risk EG0020 events0 affected90 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0021 events1 affected90 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected91 at risk EG0020 events0 affected90 at risk EG003
Pneumococcal sepsis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0021 events1 affected90 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 18.0	Non-systematic Assessment	EG0002 events2 affected92 at risk EG0012 events2 affected91 at risk EG0020 events0 affected90 at risk EG003
Hip fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Incision site haemorrhage	Injury, poisoning and procedural complications	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Fluid overload	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Transplant evaluation	Investigations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected91 at risk EG0020 events0 affected90 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0021 events1 affected90 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected91 at risk EG0022 events2 affected90 at risk EG003
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0021 events1 affected90 at risk EG003
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Intra-abdominal haemangioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0021 events1 affected90 at risk EG003
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0021 events1 affected90 at risk EG003
Cervicobrachial syndrome	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Subarachnoid haemorrhage	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0021 events1 affected90 at risk EG003
Headache	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Syncope	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0021 events1 affected90 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0021 events1 affected90 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 18.0	Non-systematic Assessment	EG0003 events3 affected92 at risk EG0014 events4 affected91 at risk EG0022 events2 affected90 at risk EG003
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected91 at risk EG0020 events0 affected90 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected91 at risk EG0021 events1 affected90 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected91 at risk EG0020 events0 affected90 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected91 at risk EG0020 events0 affected90 at risk EG003
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Catheter placement	Surgical and medical procedures	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Hypertension	Vascular disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Hypotension	Vascular disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected91 at risk EG0020 events0 affected90 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected91 at risk EG0020 events0 affected90 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiac failure chronic	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0005 events4 affected92 at risk EG0011 events1 affected91 at risk EG0025 events5 affected90 at risk EG0032 events2 affected91 at risk EG0040 events0 affected91 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0002 events2 affected92 at risk EG0016 events5 affected91 at risk EG0021 events1 affected90 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected91 at risk EG0020 events0 affected90 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0004 events3 affected92 at risk EG0016 events5 affected91 at risk EG0023 events3 affected90 at risk EG003
Asthenia	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0003 events3 affected92 at risk EG0010 events0 affected91 at risk EG0022 events2 affected90 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected91 at risk EG0022 events2 affected90 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0003 events3 affected92 at risk EG0015 events5 affected91 at risk EG0022 events2 affected90 at risk EG003
Dizziness	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0006 events5 affected92 at risk EG0013 events3 affected91 at risk EG0022 events2 affected90 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0005 events5 affected92 at risk EG0011 events1 affected91 at risk EG0023 events3 affected90 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0007 events6 affected92 at risk EG0018 events8 affected91 at risk EG0024 events4 affected90 at risk EG003
Hypotension	Vascular disorders	MedDRA 18.0	Non-systematic Assessment	EG0006 events6 affected92 at risk EG0015 events5 affected91 at risk EG0026 events5 affected90 at risk EG003

ID	Term
D006331	Heart Diseases
D002318	Cardiovascular Diseases