Phase IIb Safety and Efficacy Study of BAY94-8862 in Subjects With Worsening Chronic Heart Failure and Left Ventricular Systolic Dysfunction and Either Type 2 Diabetes Mellitus With or Without Chronic Kidney Disease or Moderate Chronic Kidney Disease Alone

Study Overview
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Brief Summary
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This study will be conducted in subjects with clinical diagnosis of worsening chronic heart failure and either type 2 diabetes mellitus (DM) with or without chronic kidney disease (CKD) or moderate CKD alone treated with evidence-based therapy for heart failure (HF) for at least 3 months prior to emergency presentation to hospital using a multi-center, randomized, adaptive, double-blind, double-dummy, comparator-controlled, parallel-group design. Primary objective of the study is to investigate efficacy [percentage of subjects with a relative decrease in N-terminal prohormone B-type natriuretic peptide (NT-proBNP) of more than 30% from baseline to Visit 10 (Day 90)] and safety of different oral doses of BAY94-8862 given once daily.

Official Title
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A Randomized, Double-blind, Double-dummy, Multi-center Study to Assess Safety and Efficacy of BAY94-8862 in Japanese Subjects With Emergency Presentation at the Hospital Because of Worsening Chronic Heart Failure With Left Ventricular Systolic Dysfunction and Either Type 2 Diabetes Mellitus With or Without Chronic Kidney Disease or Moderate Chronic Kidney Disease Alone Versus Eplerenone

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: BAY94-8862
* Drug: Eplerenone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with worsening chronic heart failure requiring emergency presentation to hospital and treatment with intravenous (IV) diuretics at hospital Subjects with either type 2 DM or moderate CKD Exclusion Criteria: Acute de-novo heart failure or acute inflammatory heart disease, e.g. acute myocarditis Acute coronary syndrome (ACS) (elevated cardiac troponins which are not caused by an ACS are not an exclusion criterion) in the last 30 days prior to the screening visit Cardiogenic shock Valvular heart disease requiring surgical intervention during the course of the study Subjects with left ventricular assistance device or waiting for heart transplantation Stroke or transient ischemic cerebral attack in the last 3 months prior to the screening visit Addison's disease

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY94-8862 (2.5 mg)<br>2.5 mg BAY94-8862 tablet and placebo capsule once daily in the morning, with possible up-titration to 5 mg once daily at Visit 6 (Day 30), and sham up-titration at Visit 8 (Day 60), based on the value of blood potassium | Drug: BAY94-8862<br>* 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg of BAY94-8862 tablets<br>Drug: Placebo<br>* matching placebo<br>|
| Experimental: BAY94-8862 (5 mg)<br>5 mg BAY94-8862 tablet and placebo capsule once daily in the morning, with possible up-titration to 10 mg once daily at Visit 6 (Day 30), and sham up-titration at Visit 8 (Day 60), based on the value of blood potassium | Drug: BAY94-8862<br>* 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg of BAY94-8862 tablets<br>Drug: Placebo<br>* matching placebo<br>|
| Active Comparator: Eplerenone<br>25 mg eplerenone every other day, i.e. one 25 mg eplerenone capsule on Day 1, Day 3, Day 5, etc. in the morning, 1 placebo capsule on Day 2, Day 4, Day 6, etc. in the morning, and 1 placebo tablet once daily in the morning, with possible up-titration to 25 mg eplerenone once daily at Visit 6 (Day 30), i.e. one 25 mg eplerenone capsule once daily in the morning and 1 placebo tablet once daily in the morning, and a possible up-titration to 25 mg once daily [if not performed at Visit 6 (Day 30)] or to 50 mg once daily [if up-titrated to 25 mg once daily at Visit 6 (Day 30)] at Visit 8 (Day 60), based on the value of blood potassium | Drug: Eplerenone<br>* INSPRA 25 and 50 mg tablets (MAH: Pfizer) will be used for eplerenone 25 and 50 mg tablets<br>Drug: Placebo<br>* matching placebo<br>|
| Experimental: BAY94-8862 (7.5 mg)<br>7.5 mg BAY94-8862 tablet and placebo capsule once daily in the morning, with possible up-titration to 15 mg once daily at Visit 6 (Day 30), and sham up-titration at Visit 8 (Day 60), based on the value of blood potassium Note: This treatment group may be introduced into the study or not after safety and tolerability of these doses has been assessed by an independent Data Monitoring Committee (DMC) (1st dose recommendation DMC meeting). | Drug: BAY94-8862<br>* 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg of BAY94-8862 tablets<br>Drug: Placebo<br>* matching placebo<br>|
| Experimental: BAY94-8862 (10 mg)<br>10 mg BAY94-8862 tablet and placebo capsule once daily in the morning, with possible up-titration to 20 mg once daily at Visit 6 (Day 30), and sham up-titration at Visit 8 (Day 60), based on the value of blood potassium Note: Only in case the above mentioned additional treatment arm (BAY94-8862, 7.5 mg) has been added, a second dose decision meeting of the DMC will take place, Again safety and tolerability of all doses will be assessed by an independent DMC (2nd dose recommendation DMC meeting). Based on this data, none or up to two treatment groups (BAY94-8862, 10 mg and BAY94-8862,15 mg) may be introduced into the study. | Drug: BAY94-8862<br>* 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg of BAY94-8862 tablets<br>Drug: Placebo<br>* matching placebo<br>|
| Experimental: BAY94-8862 (15 mg)<br>15 mg BAY94-8862 tablet and placebo capsule once daily in the morning, with possible up-titration to 20 mg once daily at Visit 6 (Day 30), and sham up-titration at Visit 8 (Day 60), based on the value of blood potassium Note: Only in case the above mentioned additional treatment arm (BAY94-8862, 7.5 mg) has been added, a second dose decision meeting of the DMC will take place, Again safety and tolerability of all doses will be assessed by an independent DMC (2nd dose recommendation DMC meeting). Based on this data, none or up to two treatment groups (BAY94-8862, 10 mg and BAY94-8862,15 mg) may be introduced into the study. | Drug: BAY94-8862<br>* 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg of BAY94-8862 tablets<br>Drug: Placebo<br>* matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of subjects with a relative decrease in N-terminal prohormone B-type natriuretic peptide of more than 30% from baseline to Visit 10 |  | From baseline to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum potassium |  | From baseline to 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BAY94-8862, MR antagonist, Heart failure, Japanese patients