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)

• ClinicalTrials.gov Identifier: NCT01951625
• Recruitment Status: Completed
• First Posted: September 26, 2013
• Last Update Posted: October 17, 2016
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: September 24, 2013
• First Posted Date: September 26, 2013
• Last Update Posted Date: October 17, 2016
• Study Start Date: November 2013
• Actual Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 24, 2013): Change in log-transformed N-terminal pro-brain natriuretic peptide (NT-proBNP) [ Time Frame: Baseline and 12 weeks ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: September 24, 2013): Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Up to 4 months ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Official Title: 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)
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Heart Failure

Intervention

• Drug: Vericiguat (BAY1021189) (1.25 mg)
  1.25 mg BAY1021189 tablets
• Drug: Vericiguat (BAY1021189) (5 mg)
  5 mg BAY1021189 tablets
• Drug: Placebo

Study Arms

• 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
  Interventions:

  • Drug: Vericiguat (BAY1021189) (1.25 mg)
  • Drug: Vericiguat (BAY1021189) (5 mg)
• 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)
  Interventions:

  • Drug: Vericiguat (BAY1021189) (1.25 mg)
  • Drug: Vericiguat (BAY1021189) (5 mg)
• Experimental: Vericiguat (BAY1021189) (2.5 mg)
  2.5 mg orally once daily for 12 weeks (with sham titrations)
  Intervention: Drug: Vericiguat (BAY1021189) (1.25 mg)
• Experimental: Vericiguat (BAY1021189) (1.25 mg)
  1.25 mg orally once daily for 12 weeks (with sham titrations)
  Intervention: Drug: Vericiguat (BAY1021189) (1.25 mg)
• Placebo Comparator: Placebo
  Orally once daily for 12 weeks (with sham titrations)
  Intervention: Drug: Placebo

Publications *

• Pieske B, Butler J, Filippatos G, Lam C, Maggioni AP, Ponikowski P, Shah S, Solomon S, Kraigher-Krainer E, Samano ET, Scalise AV, Müller 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.
• Gheorghiade M, Greene SJ, Butler J, Filippatos G, Lam CS, Maggioni AP, Ponikowski P, Shah SJ, Solomon SD, Kraigher-Krainer E, Samano ET, Müller K, Roessig L, Pieske B; SOCRATES-REDUCED Investigators and Coordinators. Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction: The SOCRATES-REDUCED Randomized Trial. JAMA. 2015 Dec 1;314(21):2251-62. doi: 10.1001/jama.2015.15734.
• Kramer F, Voss S, Roessig L, Igl BW, Butler J, Lam CSP, Maggioni AP, Shah SJ, Pieske B. Evaluation of high-sensitivity C-reactive protein and uric acid in vericiguat-treated patients with heart failure with reduced ejection fraction. Eur J Heart Fail. 2020 Mar 25. doi: 10.1002/ejhf.1787. [Epub ahead of print]

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 7, 2015): 456
• Original Estimated Enrollment (submitted: September 24, 2013): 410
• Actual Study Completion Date: June 2015
• Actual Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Bulgaria, Canada, China, Czech Republic, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT01951625
• Other Study ID Numbers: 15371; 2013-002287-11 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Bayer
• Study Sponsor: Bayer
• Collaborators: Not Provided

Investigators

• Study Director: Bayer Study Director; Bayer

• PRS Account: Bayer
• Verification Date: October 2016