BAY94-8862 Dose Finding Trial in Subjects With Chronic Heart Failure and Mild (Part A) or Moderate (Part B) Chronic Kidney Disease

Study Overview
=================
Brief Summary
-----------------
A placebo (Part A) and placebo and active comparator controlled (Part B), double-blind and randomized study to assess safety and tolerability of a new drug (BAY94-8862) given orally

Official Title
-----------------
A Randomized, Double-blind, Multi-center Study to Assess Safety and Tolerability of Different Oral Doses of BAY94-8862 in Subjects With Stable Chronic Heart Failure With Left Ventricular Systolic Dysfunction and Mild (Part A) or Moderate (Part B) Chronic Kidney Disease Versus Placebo (Part A) or Versus Placebo and Spironolactone (Part B)

Conditions
-----------------
Heart Failure

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men aged 18 years and older or postmenopausal women aged 55 years and older or women aged 18 years and older without childbearing potential based on surgical treatment such as bilateral tubal ligation, bilateral ovarectomy, or hysterectomy Clinical diagnosis of CHF (chronic heart failure), either ischemic or non-ischemic, NYHA (New York Heart Association) class II - III, treated with evidenced-based therapy for CHF, e.g. beta-blockers and ACE (angiotensin-converting enzyme) inhibitors or ARB (angiotensin receptor blocker) as well as diuretics, unless contraindicated or not tolerated Known kidney damage for >/= 3 months, as defined by structural or functional abnormalities of the kidney, and Part A: 60 mL/min/1.73 m*2 </= eGFR (estimated Glomerular Filtration Rate) < 90 mL/min/1.73 m*2 (MDRD, Modification of Diet in Renal Disease) at the screening visit Part B: 30 mL/min/1.73 m*2 </= eGFR <= 60 mL/min/1.73 m*2 (MDRD) at the screening visit Serum potassium </= 4.8 mmol/L at the screening visit Systolic blood pressure >/= 90 mmHg without signs or symptoms of hypotension at the screening visit Exclusion Criteria: Known hypersensitivity to the study drug (active substance or excipients) or spironolactone and respective excipients (Part B only) Subjects with anuria, acute renal failure, or Addison's disease Acute coronary syndrome or unstable coronary artery disease within 30 days prior to randomization Valvular heart disease requiring surgical intervention during the course of the study History of hospitalization for hyperkalemia or acute renal failure induced by previous aldosterone antagonist treatment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: BAY94-8862<br>* Two 1.25 mg BAY94-8862 and 2 placebo tablets for duration of 4 weeks<br>|
| Experimental: Arm 2<br> | Drug: BAY94-8862<br>* Four 1.25 mg BAY94-8862 tablets for duration of 4 weeks<br>|
| Experimental: Arm 3<br> | Drug: BAY94-8862<br>* One 10 mg BAY94-8862 tablet for duration of 4 weeks<br>|
| Experimental: Arm 4<br> | Drug: BAY94-8862<br>* Part B only: Four 1.25 mg BAY94-8862 tablets in the morning and four tablets in the evening for duration of 4 weeks<br>|
| Placebo Comparator: Arm 5<br> | Drug: Placebo<br>* Placebo tablets for duration of 4 weeks<br>|
| Active Comparator: Arm 6<br> | Drug: Spironolactone<br>* Part B only: 25 mg spironolactone once daily with up-titration to 50 mg once daily starting at day 15, if serum potassium is less or equal to 4.8 mmol/L, for duration of 4 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of serum potassium |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum magnesium |  | Day 8, Day 15, Day 22, Day 29 | 
| Change in blood pressure |  | Day 8, Day 15, Day 22, Day 29 | 
| Change in heart rate |  | Day 8, Day 15, Day 22, Day 29 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic Heart Failure