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)

March 2, 2021 updated by: Bayer

A Randomized Parallel-group, Placebo-controlled, Double-blind, Multi-center Dose Finding Phase II Trial Exploring the Pharmacodynamic Effects, Safety and Tolerability, and Pharmacokinetics of Four Dose Regimens of the Oral sGC Stimulator BAY1021189 Over 12 Weeks in Patients With Worsening Heart Failure With Reduced Ejection Fraction (HFrEF)

Objective of the study is to find the optimal dose of the once daily oral soluble guanylate cyclase stimulator (sGC) BAY1021189 for Phase III that can be given in addition to standard therapy for heart failure with reduced ejection fraction (HFrEF).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

456

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Darlinghurst, New South Wales, Australia, 2010
    • Tasmania
      • Hobart, Tasmania, Australia, 7000
    • Victoria
      • Prahran, Victoria, Australia, 3181
  • Austria
      • Salzburg, Austria, 5020
      • Wien, Austria, 1220
    • Niederösterreich
      • St. Pölten, Niederösterreich, Austria, 3100
    • Oberösterreich
      • Linz, Oberösterreich, Austria, 4020
    • Steiermark
      • Graz, Steiermark, Austria, 8036
  • Belgium
      • Brugge, Belgium, 8000
      • Bruxelles - Brussel, Belgium, 1200
      • Gent, Belgium, 9000
      • Gilly, Belgium, 6060
      • HUY, Belgium, 4500
      • MOL, Belgium, 2400
      • Mechelen, Belgium, 2800
      • Roeselare, Belgium, 8800
  • Bulgaria
      • Sofia, Bulgaria, 1233
      • Sofia, Bulgaria, 1527
      • Sofia, Bulgaria, 1202
      • Sofia, Bulgaria, 1309
      • Stara Zagora, Bulgaria, 6000
  • Canada
      • Quebec, Canada, G1V 4G5
    • Ontario
      • Toronto, Ontario, Canada, M5B 1W8
    • Quebec
      • Montreal, Quebec, Canada, H1T 1C8
      • Montreal, Quebec, Canada, H2W 1T8
      • Saint-Jean-sur-Richelieu, Quebec, Canada, J3A 1C3
      • Sherbrooke, Quebec, Canada, J1G 2E8
  • Czechia
      • Hradec kralove, Czechia, 500 05
      • Kromeriz, Czechia, 767 01
      • Ostrava, Czechia, 708 52
        • Fakultni nemocnice Ostrava
      • Praha 10, Czechia, 10034
      • Praha 2, Czechia, 12808
      • Praha 4, Czechia, 140 21
      • Praha 6, Czechia, 169 02
      • Slany, Czechia, 274 01
  • Denmark
      • Aalborg, Denmark, 9000
      • Aarhus N, Denmark, 8200
      • Hellerup, Denmark, DK-2900
      • Viborg, Denmark, 8800
  • France
      • BRON Cedex, France, 69677
      • La Tronche, France, 38700
      • Lille Cedex, France, 59037
      • Paris Cedex 15, France, 75908
      • Pessac, France, 33604
      • Rouen, France, 76031
  • Germany
      • Hamburg, Germany, 20246
    • Bayern
      • München, Bayern, Germany, 80331
    • Hessen
      • Bad Homburg, Hessen, Germany, 61348
      • Frankfurt, Hessen, Germany, 60596
    • Mecklenburg-Vorpommern
      • Greifswald, Mecklenburg-Vorpommern, Germany, 17475
    • Niedersachsen
      • Hannover, Niedersachsen, Germany, 30625
    • Nordrhein-Westfalen
      • Köln, Nordrhein-Westfalen, Germany, 50924
      • Münster, Nordrhein-Westfalen, Germany, 48149
    • Saarland
      • Homburg, Saarland, Germany, 66424
    • Thüringen
      • Erfurt, Thüringen, Germany, 99089
  • Greece
      • Athens, Greece, 11527
      • Nea Ionia, Greece, 14233
  • Hungary
      • Budapest, Hungary, 1032
      • Kistarcsa, Hungary, H-2143
      • Szekesfehervar, Hungary, 8000
  • Israel
      • Afula, Israel, 1834111
      • Ashkelon, Israel, 7830604
      • Hadera, Israel, 3810101
      • Jerusalem, Israel, 9103102
      • Petah Tikva, Israel, 4941492
      • Rehovot, Israel, 7610001
      • Tel Aviv, Israel, 6423906
      • Tiberias, Israel, 1528001
      • Zrifin, Israel, 7030000
  • Italy
    • Lombardia
      • Bergamo, Lombardia, Italy, 24127
      • Brescia, Lombardia, Italy, 25123
      • Como, Lombardia, Italy, 22020
      • Milano, Lombardia, Italy, 20017
      • Milano, Lombardia, Italy, 20138
      • Milano, Lombardia, Italy, 20149
      • Pavia, Lombardia, Italy, 27100
    • Marche
      • Ancona, Marche, Italy, 60126
    • Toscana
      • Arezzo, Toscana, Italy, 52040
    • Veneto
      • Verona, Veneto, Italy, 37045
  • Japan
      • Fukui, Japan, 910-8526
      • Hiroshima, Japan, 734-8530
      • Kumamoto, Japan, 862-8505
      • Nagasaki, Japan, 850-8555
      • Tokushima, Japan, 770-8539
      • Toyama, Japan, 930-8550
    • Fukuoka
      • Iizuka, Fukuoka, Japan, 820-8505
    • Hyogo
      • Himeji, Hyogo, Japan, 670-0981
    • Ishikawa
      • Kanazawa, Ishikawa, Japan, 920-8650
    • Kanagawa
      • Sagamihara, Kanagawa, Japan, 252-5188
      • Yokohama, Kanagawa, Japan, 236-0051
      • Yokosuka, Kanagawa, Japan, 238-8567
    • Miyagi
      • Sendai, Miyagi, Japan, 981-3133
    • Okinawa
      • Naha, Okinawa, Japan, 902-8511
    • Osaka
      • Takatsuki, Osaka, Japan, 569-1096
      • Yao, Osaka, Japan, 581-0011
    • Saga
      • Ureshino, Saga, Japan, 843-0393
    • Tokushima
      • Komatsushima, Tokushima, Japan, 773-8502
    • Tokyo
      • Meguro-ku, Tokyo, Japan, 152-8902
      • Minato-ku, Tokyo, Japan, 106-0031
  • Korea, Republic of
      • Seoul, Korea, Republic of, 138-736
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
      • Deventer, Netherlands, 7416 SE
      • Heerenveen, Netherlands, 8441 PW
      • Leeuwarden, Netherlands, 8901 BR
      • Veldhoven, Netherlands, 5504 DB
  • Poland
      • Bialystok, Poland, 15-276
      • Krakow, Poland, 31-202
      • Legnica, Poland, 59-220
      • Lodz, Poland, 92-213
      • Olsztyn, Poland, 10-010
      • Poznan, Poland, 61-848
      • Warszawa, Poland, 02-507
  • Singapore
      • Singapore, Singapore, 119228
      • Singapore, Singapore, 308433
      • Singapore, Singapore, 169609
      • Singapore, Singapore, 768828
  • Spain
      • Barcelona, Spain, 08003
      • Barcelona, Spain, 08023
      • Valencia, Spain, 46026
      • Valencia, Spain, 46010
    • Barcelona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
    • Cantabria
      • Santander, Cantabria, Spain, 39008
    • Madrid
      • Majadahonda, Madrid, Spain, 28222
  • Sweden
      • Helsingborg, Sweden, 251 87
      • Karlstad, Sweden, 651 85
      • Linköping, Sweden, 581 85
      • Malmö, Sweden, 205 02
      • Stockholm, Sweden, 118 83
      • Örebro, Sweden, 701 85
  • Switzerland
      • Bruderholz, Switzerland, 4101
      • Lugano, Switzerland, 6900
      • Zürich, Switzerland, 8091
    • Basel-Landschaft
      • Liestal, Basel-Landschaft, Switzerland, 4410
  • Taiwan
      • Kaohsiung, Taiwan, 813
      • New Taipei City, Taiwan, 220
      • Taipei, Taiwan, 11217
      • Taipei, Taiwan, 10016
  • United Kingdom
    • Derbyshire
      • Chesterfield, Derbyshire, United Kingdom, S44 5DX
    • Hertfordshire
      • Stevenage, Hertfordshire, United Kingdom, SG1 4AB
  • United States
    • California
      • Fountain Valley, California, United States, 92708
    • Delaware
      • Wilmington, Delaware, United States, 19803
    • Florida
      • Fort Lauderdale, Florida, United States, 33308
      • Jacksonville, Florida, United States, 32209
      • Naples, Florida, United States, 34102
    • Georgia
      • Atlanta, Georgia, United States, 30342
      • Macon, Georgia, United States, 31201
    • Louisiana
      • New Orleans, Louisiana, United States, 70112-1396
    • Michigan
      • Detroit, Michigan, United States, 48202
    • Minnesota
      • Minneapolis, Minnesota, United States, 55422
    • Mississippi
      • Jackson, Mississippi, United States, 39216-4505
    • New York
      • Buffalo, New York, United States, 14215
    • Ohio
      • Columbus, Ohio, United States, 43210
      • Fairfield, Ohio, United States, 45014
    • South Carolina
      • Charleston, South Carolina, United States, 29425
    • Tennessee
      • Germantown, Tennessee, United States, 38138
      • Nashville, Tennessee, United States, 37232-8802
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53215

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Worsening chronic heart failure (WCHF) requiring hospitalization (or intravenous diuretic treatment for HF without hospitalization) with initiation of study treatment after clinical stabilization
  • Left ventricular ejection fraction (LVEF) <45% by echocardiography at randomization

Exclusion Criteria:

  • Intravenous inotropes at any time after hospitalization

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vericiguat (BAY1021189) (10 mg)
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)
1.25 mg BAY1021189 tablets
Drug: Vericiguat (BAY1021189) (5 mg)
5 mg BAY1021189 tablets
Experimental: Vericiguat (BAY1021189) (5 mg)
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)
1.25 mg BAY1021189 tablets
Drug: Vericiguat (BAY1021189) (5 mg)
5 mg BAY1021189 tablets
Experimental: Vericiguat (BAY1021189) (2.5 mg)
2.5 mg orally once daily for 12 weeks (with sham titrations)
Drug: Vericiguat (BAY1021189) (1.25 mg)
1.25 mg BAY1021189 tablets
Experimental: Vericiguat (BAY1021189) (1.25 mg)
1.25 mg orally once daily for 12 weeks (with sham titrations)
Drug: Vericiguat (BAY1021189) (1.25 mg)
1.25 mg BAY1021189 tablets
Placebo Comparator: Placebo
Orally once daily for 12 weeks (with sham titrations)
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) to Week 12
Time Frame: Baseline, 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 Outcome Measures

Outcome Measure
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
Time Frame: Baseline, 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
Changes in Heart Function as Measured by Echocardiography, Left Ventricular Ejection Fraction (LVEF), From Baseline to Week 12
Time Frame: Baseline, 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.
Baseline, Week 12
Change From Baseline in Systolic and Diastolic Blood Pressure to Week 12
Time Frame: Baseline, 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.
Baseline, Week 12
Change From Baseline in Heart Rate to Week 12
Time Frame: Baseline, 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.
Baseline, Week 12
Number of Subjects With Clinical Events (Heart Failure [HF] Hospitalization and Cardio-Vascular [CV] Mortality)
Time Frame: Baseline until 16 weeks
Clinical events (heart failure and mortality) were analyzed as CV death, and HF hospitalization at specified time points.
Baseline until 16 weeks
Number of Subjects With Implantable Cardioverter Defibrillators Cardiac Resynchronization Therapy With Defibrillation (ICD/CRT-D) Therapy
Time Frame: Baseline upto 16 weeks
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.
Baseline upto 16 weeks
Number of Subjects With Treatment-Emergent Adverse Events
Time Frame: From the start of study treatment upto 5 days after the last dose of study drug
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.
From the start of study treatment upto 5 days after the last dose of study drug
Change in Biomarkers From Baseline to Week 12: Osteopontin (ng/mL)
Time Frame: Baseline, Week 12
Baseline, Week 12
Change in Biomarkers From Baseline to Week 12: TIMP-4 (pg/mL)
Time Frame: Baseline, Week 12
TIMP-4: tissue inhibitor of matrix metalloproteinases 4
Baseline, Week 12
Change in Biomarkers From Baseline to Week 12: cGMP (Pmol/mL)
Time Frame: Baseline, Week 12
cGMP: cyclic guanosine monophosphate
Baseline, Week 12
Change in Biomarkers From Baseline to Week 12: PIIINP (mcg/L)
Time Frame: Baseline, Week 12
PIIINP: pro-collagen III N-terminal peptide
Baseline, Week 12
Change in Biomarkers From Baseline to Week 12: GDF-15 (pg/mL)
Time Frame: Baseline, Week 12
GDF-15: growth differentiation factor 15
Baseline, Week 12
Change in Biomarkers From Baseline to Week 12: ST2 (pg/mL)
Time Frame: Baseline, Week 12
ST2: suppression of tumorigenicity 2
Baseline, Week 12
Change in Biomarkers From Baseline to Week 12: Gal-3 (μg/mL)
Time Frame: Baseline, Week 12
Gal-3: Galectin-3
Baseline, Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bayer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 29, 2013

Primary Completion (Actual)

May 14, 2015

Study Completion (Actual)

June 9, 2015

Study Registration Dates

First Submitted

September 24, 2013

First Submitted That Met QC Criteria

September 24, 2013

First Posted (Estimate)

September 26, 2013

Study Record Updates

Last Update Posted (Actual)

March 25, 2021

Last Update Submitted That Met QC Criteria

March 2, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15371
  • 2013-002287-11 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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