Phase IIb Safety and Efficacy Study of Different Oral Doses 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 Chronic Kidney Disease Alone

Phase 2

Completed

• Conditions: Heart Failure
• Interventions: Drug: Finerenone (BAY94-8862); Drug: Placebo; Drug: Inspra (eplerenone)

• Registration Number: NCT01807221
• Lead Sponsor: Bayer

Brief Summary

To assess a new drug, BAY94-8862, given orally at different doses, to evaluate whether it was safe and can help the well-being of patients with worsening chronic heart failure and either type II diabetes with or without chronic kidney disease or kidney disease alone. These treatment doses were compared to eplerenone, another marketed drug approved to treat heart failure.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-03-07
• Study First Submitted QC: 2013-03-07
• Study First Posted: 2013-03-08
• Study Start: 2013-06-17
• Primary Completion: 2014-11-11
• Study Completion: 2014-12-09
• Disposition First Submitted: 2015-06-04
• Disposition First Submitted QC: 2015-06-04
• Disposition First Posted: 2015-07-01
• Results First Submitted: 2021-04-15
• Results First Submitted QC: 2021-05-20
• Results First Posted: 2021-06-15
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-02
• Last Update Posted: 2021-07-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1066

Inclusion Criteria

• Men and women aged 18 years and older. The lower age limit may be higher if legally required in the participating country
• Women of childbearing potential can only be included in the study if a pregnancy test is negative and if they agree to use adequate contraception when sexually active
• Subjects with worsening chronic heart failure requiring emergency presentation to hospital and treatment with intravenous diuretics at hospital
• Subjects with clinical diagnosis of chronic heart failure (CHF) either ischemic or non ischemic, New York Heart Association (NYHA) functional class II-IV
• Subjects with type 2 diabetes mellitus and / or
• Subjects with 30 mL/min/1.73m^2 </= eGFR </= 60 mL/min/1.73m^2 (MDRD, Modification of Diet in Renal Disease Study Group) at screening
• Left ventricular ejection fraction (LVEF) </= 40%
• Blood potassium </= 5.0 mmol/L at screening
• Systolic blood pressure >/= 90 mmHg without signs and symptoms of hypotension at the screening visit

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Exclusion Criteria

• Acute de-novo heart failure or acute inflammatory heart disease, e.g. acute myocarditis
• Acute coronary syndrome (ACS) in last 30 days prior to screening
• Cardiogenic shock
• Valvular heart disease requiring surgical intervention during the course of the study
• Stroke or transient ischemic cerebral attack in the last 3 months prior to the screening visit
• Concomitant treatment with any mineralocorticoid receptor antagonist (MRA), renin inhibitor, or potassium-sparing diuretic

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Finerenone(BAY94-8862)[2.5mg] + Placebo	Finerenone (BAY94-8862)	Oral - 2.5mg once daily (OD) for 30 days. Potential up-titration to 5mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Finerenone(BAY94-8862)[2.5mg] + Placebo	Placebo	Oral - 2.5mg once daily (OD) for 30 days. Potential up-titration to 5mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Finerenone (BAY94-8862)[5mg] + Placebo	Placebo	Oral - 5mg OD for 30 days. Potential up-titration to 10 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Finerenone (BAY94-8862)[7.5mg] + Placebo	Placebo	Oral - 7.5mg OD for 30 days. Potential up-titration to 15 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Finerenone (BAY94-8862)[10mg] + Placebo	Placebo	Oral - 10mg OD for 30 days. Potential up-titration to 20 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Finerenone (BAY94-8862)[15mg] + Placebo	Placebo	Oral - 15mg OD for 30 days. Potential up-titration to 20 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Eplerenone [25 mg] + Placebo	Placebo	Oral - 25mg every other day (EOD). Potential up-titration to 25mg OD after 30 days and 50mg OD after 60 days.Placebo OD for 90 days.
Finerenone (BAY94-8862)[15mg] + Placebo	Finerenone (BAY94-8862)	Oral - 15mg OD for 30 days. Potential up-titration to 20 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Finerenone (BAY94-8862)[5mg] + Placebo	Finerenone (BAY94-8862)	Oral - 5mg OD for 30 days. Potential up-titration to 10 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Finerenone (BAY94-8862)[10mg] + Placebo	Finerenone (BAY94-8862)	Oral - 10mg OD for 30 days. Potential up-titration to 20 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Finerenone (BAY94-8862)[7.5mg] + Placebo	Finerenone (BAY94-8862)	Oral - 7.5mg OD for 30 days. Potential up-titration to 15 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Eplerenone [25 mg] + Placebo	Inspra (eplerenone)	Oral - 25mg every other day (EOD). Potential up-titration to 25mg OD after 30 days and 50mg OD after 60 days.Placebo OD for 90 days.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With a Relative Decrease in NT-proBNP of More Than 30% From Baseline to Day 90	Baseline and Day 90	N-terminal pro-B type natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute and chronic heart failure (CHF) and may be useful to establish prognosis in heart failure.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Death Due to Any Cause	Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)	Death due to any cause include cardiovascular (CV) death and Non-CV death. Non-CV death was classified by 2 subcategories: non-malignant causes and malignant causes.
Change From Baseline in KCCQ Questionnaire Scores at Specified Visits	Baseline, Day 30 and Day 90	The Kansas City Cardiomyopathy Questionnaire (KCCQ) was the leading health related quality of life measure for subjects with CHF. KCCQ was a 23 item questionnaire that independently measures the impact of subjects HF, or its treatment, on 7 distinct domains: self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. KCCQ clinical summary score is a composite assessment of physical limitations and total symptom scores. Results from the total symptom summary score are presented. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. In the below table, categorical data represents change from baseline data at respective time points.
Number of Participants With Cardiovascular Hospitalization	Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)	Hospitalizations were defined as any unplanned admission to hospital, i.e. completion of hospital admission procedures and one overnight \[i.e. date change\] stay or until the death of subject occurred. Hospitalizations and deaths were classified by 2 primary categories: CV and non-CV. The pre-specified subcategories for CV hospitalizations were as follows: 1. Worsening heart failure, 2.Acute myocardial infarction, 3. Arrhythmia, 4.Transient ischemic attack and stroke, 5. Other CV hospitalizations.
Number of Participants With Emergency Presentations for Worsening Chronic Heart Failure (WCHF)	Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)	Emergency presentations for WCHF were defined as newly developing signs and symptoms of WCHF after start of treatment with study drug, requiring an additional emergency presentation to hospital and IV treatment with diuretics and/or positive inotropic agents.
Ratio of BNP at Specified Visits to BNP at Baseline	Day 30, Day 60, Day 90, Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120)	B-type natriuretic peptide (BNP) levels in the blood are used for screening, diagnosis of acute chronic heart failure (CHF) and may be useful to establish prognosis in heart failure.
Ratio of NT-proBNP at Specified Visits to NT-proBNP at Baseline	Day 30, Day 60, Day 90, Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120)	N-terminal pro-B type natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute chronic heart failure (CHF) and may be useful to establish prognosis in heart failure.
Change From Baseline in EQ-5D-3L Questionnaire Scores at Specified Visits	Baseline, Day 30, Day 90, Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120)	EuroQol Group 5-Dimension, 3-Level (EQ-5D-3L): participant rated questionnaire to assess health-related quality of life. It consists of EQ-5D descriptive system and EQ-5D Visual Analog Scale (VAS). EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems (1), some problems (2), and extreme problems (3). For this population, the possible EQ-5D-3L index scores ranges from -0.11 (that is, 3 for all 5 dimensions) to 1.0 (that is, 1 for all 5 dimensions), where higher scores indicate a better health state.