A Trial to Study Neladenoson Bialanate Over 20 Weeks in Patients With Chronic Heart Failure With Preserved 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 (BAY1067197) when given in addition to appropriate therapy for specific comorbidities.

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, Pharmacokinetics and Pharmacodynamic Effects of the Oral Partial Adenosine A1 Receptor Agonist Neladenoson Bialanate Over 20 Weeks in Patients With Chronic Heart Failure and Preserved 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 45 years and older Diagnosis of chronic heart failure, NYHA (New York Heart Association) class II-IV, LVEF (left ventricular ejection fraction) ≥ 45% and elevated NT-proBNP Exclusion Criteria: Acute decompensated heart failure within the past 4 weeks Inability to exercise Previous diagnosis of HFrEF (heart failure with reduced ejection fraction) (LVEF < 40%)

Ages Eligible for Study
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Minimum Age: 45 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 preserved 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 preserved 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 preserved 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 preserved 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 preserved ejection fraction | Drug: Neladenoson bialanate (BAY1067197)<br>* 40 mg orally once daily for 20 weeks<br>|
| Placebo Comparator: Placebo<br>Chronic heart failure with preserved 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 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment | The 6MWD test is designed to evaluate a subject's exercise capacity while performing an everyday activity. | Baseline, and up to 20 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity | AVIVO™ Mobile Patient Management System, a wearable wireless device worn by the subject, was used to monitor subjects' cardiovascular status. The patient's everyday physical activity e.g. duration, intensity, was also tracked by the AVIVO device. For Activity Intensity, the Unit of Measure is percentage of maximum activity, and length of intervals is daily. | Baseline, and up to 20 weeks of treatment | 
| Measured Values (Log Transformed) and Absolute Change in NT-proBNP From Baseline to 20 Weeks | NT-proBNP = N-terminal pro-hormone b-type natriuretic peptide | Baseline, and up to 20 weeks of treatment | 
| Measured Values (Log-transformed) and Absolute Change in High Sensitivity Troponin T (Hs-TNT) From Baseline to 20 Weeks | High sensitivity troponin T (hs-TNT) was measured | Baseline, and up to 20 weeks of treatment | 
| Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | The KCCQ is the leading health-related quality-of-life measure for patients with chronic heart failure (CHF). It is a 23-item questionnaire that independently measures the impact of patient's heart failure (HF), or its treatment, on 7 distinct domains: 1) Symptom Frequency 2) Symptom Burden 3) Physical Limitation 4) Quality of Life 5) Social Limitations 6) Self-efficacy 7) Symptoms Stability. Overall summary score= mean score of (symptom frequency + symptom burden+ physical limitation + quality of life + social limitation); scores on a scale of 0 to 100, higher scores means better outcome; Physical Limitation: scores on a scale of 0 to 100, higher scores means better outcome; Total symptom score=mean score of (symptom frequency + symptom burden): scores on a scale of 0 to 100, higher scores means better outcome. Positive change means improvement and negative change means deterioration. | Baseline, and up to 20 weeks of treatment | 

 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 Preserved Ejection Fraction