Study to Investigate the Natriuretic Effects, Safety, Tolerability and Pharmacokinetics of BAY94-8862

Study Overview
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Brief Summary
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Pharmacodynamics, pharmacokinetics, safety, and tolerability will be investigated in this single dose study. In 5 treatment groups, different dosages of BAY94-8862 will be given in healthy male subjects.

Detailed Description
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Clinical pharmacology

Official Title
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Study to Investigate the Effectiveness of Different Single Oral Doses of BAY94-8862 on Natriuresis After Administration of 0.5 mg Fludrocortisone (Astonin H®) With 50 mg Eplerenone (Inspra®) as Active Control in Healthy Male Subjects in a Randomized, Single-blind, Placebo-controlled, Combined 3-fold Crossover and Parallel-group Design

Conditions
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Clinical Pharmacology

Intervention / Treatment
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* Drug: Finerenone (BAY 94-8862) PEG solution
* Drug: Finerenone (BAY 94-8862) immediate release tablet
* Drug: Eplerenone (Inspra®)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male white subjects 18 to 46 years of age Body mass index (BMI): 18 - 29.9 kg/m² Exclusion Criteria: Clinically relevant findings in medical history or in the physical examination Systolic blood pressure below 100 or above 140 mmHg Diastolic blood pressure below 50 or above 90 mmHg Heart rate below 45 or above 95 beats / min

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 46 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Finerenone (20 mg solution)<br>3-fold crossover of single dose 20 mg BAY 94-8862 solution, placebo and 50 mg eplerenone. The challenge drug fludrocortisone was given 2 h prior to administration of BAY 94-8862, eplerenone, and placebo. | Drug: Finerenone (BAY 94-8862) PEG solution<br>* 2.5, 5, 10, 20 mg polyethylene glycol (PEG) solution of BAY 94-8862<br>Drug: Eplerenone (Inspra®)<br>* Single oral dose of 50 mg eplerenone<br>Drug: Placebo<br>* Matching placebo (solution/tablet) corresponding to BAY 94-8862 dose in respective dose step<br>|
| Experimental: Finerenone (10 mg solution)<br>3-fold crossover of single dose 10 mg BAY 94-8862 solution, placebo and 50 mg eplerenone. The challenge drug fludrocortisone was given 2 h prior to administration of BAY 94-8862, eplerenone, and placebo. | Drug: Finerenone (BAY 94-8862) PEG solution<br>* 2.5, 5, 10, 20 mg polyethylene glycol (PEG) solution of BAY 94-8862<br>Drug: Eplerenone (Inspra®)<br>* Single oral dose of 50 mg eplerenone<br>Drug: Placebo<br>* Matching placebo (solution/tablet) corresponding to BAY 94-8862 dose in respective dose step<br>|
| Experimental: Finerenone (5 mg solution)<br>3-fold crossover of single dose 5 mg BAY 94-8862 solution, placebo and 50 mg eplerenone. The challenge drug fludrocortisone was given 2 h prior to administration of BAY 94-8862, eplerenone, and placebo. | Drug: Finerenone (BAY 94-8862) PEG solution<br>* 2.5, 5, 10, 20 mg polyethylene glycol (PEG) solution of BAY 94-8862<br>Drug: Eplerenone (Inspra®)<br>* Single oral dose of 50 mg eplerenone<br>Drug: Placebo<br>* Matching placebo (solution/tablet) corresponding to BAY 94-8862 dose in respective dose step<br>|
| Experimental: Finerenone (20 mg as tablets)<br>3-fold crossover of single dose 20 mg BAY 94-8862 as 2 x 10 mg tablet, placebo and 50 mg eplerenone. The challenge drug fludrocortisone was given 2 h prior to administration of BAY 94-8862, eplerenone, and placebo. | Drug: Finerenone (BAY 94-8862) immediate release tablet<br>* 20 mg BAY 94-8862 administered as 2 x 10 mg IR tablets<br>Drug: Eplerenone (Inspra®)<br>* Single oral dose of 50 mg eplerenone<br>Drug: Placebo<br>* Matching placebo (solution/tablet) corresponding to BAY 94-8862 dose in respective dose step<br>|
| Experimental: Finerenone (2.5 mg solution)<br>3-fold crossover of single dose 2.5 mg BAY 94-8862 solution, placebo and 50 mg eplerenone. The challenge drug fludrocortisone was given 2 h prior to administration of BAY 94-8862, eplerenone, and placebo. | Drug: Finerenone (BAY 94-8862) PEG solution<br>* 2.5, 5, 10, 20 mg polyethylene glycol (PEG) solution of BAY 94-8862<br>Drug: Eplerenone (Inspra®)<br>* Single oral dose of 50 mg eplerenone<br>Drug: Placebo<br>* Matching placebo (solution/tablet) corresponding to BAY 94-8862 dose in respective dose step<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Log10 (10*urinary Na+/K+ ratio) (Parameter for natriuresis) |  | Up to 26 hours post-dose | 
| AUC (Area under the concentration vs time curve from zero to infinity after single (first) dose for both BAY 94-8862 and eplerenone) |  | Up to 60 hours after administration | 
| Cmax (Maximum observed drug concentration in measured matrix after single dose administration for both BAY 94-8862 and eplerenone) |  | Up to 60 hours after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events |  | Up to 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy volunteers, proof-of-concept trial, PK and PD