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

Study Overview
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Brief Summary
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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 diuretic and comorbidity treatment for heart failure with preserved ejection fraction (HFpEF)

Official Title
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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 and Preserved Ejection Fraction (HFpEF)

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Vericiguat (BAY1021189) (1.25 mg)
* Drug: Vericiguat (BAY1021189) (5 mg)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in Log-transformed N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) | NTproBNP is a circulating plasma biomarker of cardiovascular function and prognosis in heart failure (HF). | Baseline, Week 12 (end of treatment [EOT]) | 
| Change From Baseline to Week 12 in Left Atrial Volume (LAV) | Left atrial volume was measured by echocardiography. | Baseline, Week 12 (EOT) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Worsening Heart Failure, Heart Failure with Preserved Ejection Fraction