A Trial to Study Neladenoson Bialanate Over 20 Weeks in Patients With Chronic Heart Failure With Reduced Ejection Fraction

Study Overview
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Brief Summary
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The objective of the study is to find the optimal dose of once daily oral neladenoson bialanate (BAY 1067197) when given in addition to standard therapy for heart failure with reduced ejection fraction (HFrEF).

Official Title
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A Multicenter, Randomized, Placebo-controlled, Parallel Group, Double Blind, Dose-finding Phase II Trial to Study the Efficacy, Safety, Pharmacokinetic and Pharmacodynamic Effects of the Oral Partial Adenosine A1 Receptor Agonist Neladenoson Bialanate Over 20 Weeks in Patients With Chronic Heart Failure With Reduced Ejection Fraction

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Neladenoson bialanate (BAY1067197)
* Drug: Neladenoson bialanate (BAY1067197)
* Drug: Neladenoson bialanate (BAY1067197)
* Drug: Neladenoson bialanate (BAY1067197)
* Drug: Neladenoson bialanate (BAY1067197)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women aged 18 years and older Diagnosis of chronic heart failure (CHF), NYHA ( New York Heart Association ) class II-IV, LVEF ≤ 35% and elevated NT-proBNP Exclusion Criteria: Acute de-novo heart failure Requirement of any intravenous (IV) treatments following 48 hours prior to randomization Mechanical support (e.g. intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device) Any cause of chronic heart failure other than ischemic cardiomyopathy and idiopathic dilated cardiomyopathy

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: Neladenoson bialanate (BAY1067197) (5 mg)<br>Chronic heart failure with reduced ejection fraction | Drug: Neladenoson bialanate (BAY1067197)<br>* 5 mg orally once daily for 20 weeks<br>|
| Experimental: Neladenoson bialanate (BAY1067197) (10 mg)<br>Chronic heart failure with reduced ejection fraction | Drug: Neladenoson bialanate (BAY1067197)<br>* 10 mg orally once daily for 20 weeks<br>|
| Experimental: Neladenoson bialanate (BAY1067197) (20 mg)<br>Chronic heart failure with reduced ejection fraction | Drug: Neladenoson bialanate (BAY1067197)<br>* 20 mg orally once daily for 20 weeks<br>|
| Experimental: Neladenoson bialanate (BAY1067197) (30 mg)<br>Chronic heart failure with reduced ejection fraction | Drug: Neladenoson bialanate (BAY1067197)<br>* 30 mg orally once daily for 20 weeks<br>|
| Experimental: Neladenoson bialanate (BAY1067197) (40 mg)<br>Chronic heart failure with reduced ejection fraction | Drug: Neladenoson bialanate (BAY1067197)<br>* 40 mg orally once daily for 20 weeks<br>|
| Placebo Comparator: Placebo<br>Chronic heart failure with reduced ejection fraction | Drug: Placebo<br>* Orally once daily for 20 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Left Ventricular Ejection Fraction (LVEF) (%) at Week 20 Measured by Echocardiography | Left ventricular ejection fraction (LVEF) was measured by echocardiography. Mean and standard deviation were reported. | Baseline, Week 20 | 
| Absolute Change From Baseline in Log-transformed NT-pro B-type Natriuretic Peptide (BNP) at Week 20 | NT-pro b-type Natriuretic Peptide (BNP) was measured. Mean and standard deviation were reported. | Baseline, Week 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Left Ventricular End-Systolic Volume (LVESV) at Week 20 | LVESV was defined as the volume of blood in the left ventricle at the end of contraction, or systole and the beginning of filling or diastole. Mean and standard deviation were reported. | Baseline, Week 20 | 
| Change From Baseline in Left Ventricular End-Diastolic Volume (LVEDV) at Week 20 | LVEDV was defined as the volume of blood in the left ventricle at end load or filling in diastole or the amount of blood in the ventricles just before systole. Mean and standard deviation were reported. | Baseline, Week 20 | 
| Change From Baseline in High Sensitivity Troponin T (Hs-TNT) at Week 20 | High sensitivity troponin T (hs-TNT) was measured. Mean and standard deviation were reported. | Baseline, Week 20 | 
| Number of Participants With Composite Efficacy Outcome | Composite efficacy outcome was the first occurrence of CV death, HF hospitalization or urgent visit for HF. Number of participants with composite efficacy outcome were reported. | Baseline up to Week 26 | 
| Number of Participants With Cardiovascular (CV) Mortality | Cardiovascular (CV) mortality was assessed. Number of participants with CV mortality were reported. | Baseline up to Week 26 | 
| Number of Participants With Heart Failure (HF) Hospitalization and Urgent Visits for Heart Failure (HF) | Number of participants with HF hospitalization and urgent visits for HF were reported. | Baseline up to Week 26 | 

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