A Study to Learn How BAY94-8862 Moves Into, Through and Out of the Body, How Safe it is and How it Affects the Body in Adult Participants With Reduced Kidney Function and in Healthy Participants With Similar Age, Weight and Gender Distribution

Investigation of Pharmacokinetics, Safety, and Tolerability of BAY 94-8862 in Male and Female Subjects With Renal Impairment and in Age- and Weight-matched Healthy Subjects Following a Single Oral Dose of 10 mg BAY 94-8862 IR Tablet in a Single-center, Non-randomized, Non-controlled, Non-blinded, Observational Study With Group Stratification

Researchers are looking for a better way to treat people who have worsening of chronic heart failure, a long-term condition where the heart does not pump blood as well as it should.

In this study researchers wanted to learn more about a new substance called finerenone (BAY94-8862).

Finerenone is a substance that blocks the activation of a protein in the body called mineralocorticoid receptor (MR). An increased activation of MR is involved in the development of hypertension, organ damage and worsening of heart failure. Many patients with worsening chronic heart failure also suffer from chronic kidney disease. Chronic kidney disease is a long-term decrease in the kidneys' ability to work properly.

The researchers studied how finerenone moves into, through and out of the body. The researchers also looked at how safe finerenone is and how it affects the body. The main purpose of this study was to help researchers develop recommendations for the amount of the substance (the dosing) to be given to patients with reduced kidney function.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; Worsening Chronic Heart Failure
• Intervention / Treatment: Drug: Finerenone (BAY94-8862)

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The informed consent must be signed before any study specific tests or procedures are done;
• Male participants and female participants without childbearing potential (postmenopausal women with 12 month of spontaneous amenorrhea or with 6 month of spontaneous amenorrhea and serum follicle-stimulating hormone (FSH) levels >30 mIU/mL; women with 6 weeks post bilateral ovarectomy, women with bilateral tubal ligation, and women with hysterectomy);
• Age: 18 to 79 years at the first screening examination;
• Race: White;
• Body mass index (BMI): ≥ 18 and ≤ 34 kg / m2;

Participants with renal impairment

• Creatinine clearance (CLCR) ≤ 80 mL/min determined from a 24 hour urine collection interval 2 - 14 days prior to dosing;
• Stable renal disease, ie a serum creatinine value determined at least 3-6 months before the pre-study visit should not vary by more than 20% from the serum creatinine value determined at the pre-study visit;

Healthy participants

- Mean age and body weight in Group 1 (control group, healthy participants) and Groups 2 - 4 should not vary by more than +/- 10 years and +/- 10 kg, respectively.

Exclusion Criteria:

• Participation in another clinical trial during the preceding 3 months for multiple dose studies and 1 month for single-dose studies; (final examination from previous study to first treatment of new study);
• Exclusion periods from other studies or simultaneous participation in other clinical studies;
• Donation of more than 100 mL of blood within 4 weeks before the first study drug administration or more than 500 mL in the preceding 3 months;

• Regular use of following medication during or within the 1 - 2 weeks preceding the study:

  • concomitant administration of other Aldosterone-antagonists (eg. eplerenone or spironolactone), potassium-sparing diuretics, potassium supplements, nonsteroidal anti-inflammatory drugs like ASS (secondary prevention with a dose of 100 mg daily is allowed), indomethacin or ibuprofen
  • concomitant use of cytochrome P450 isoenzyme 3A4 (CYP3A4) inducers (eg St. John´s wort, rifampicin, carbamazepin, phenytoin, phenobarbital, bosentan)
  • concomitant use of weak to moderate CYP3A4 inhibitors (eg erythromycin, quinupristin/dalfopristin, saquinavir, fluconazole, amiodarone, diltiazem, fluvoxamine, verapamil, valproic acid, fluoxetine, grapefruit juice)
  • strong inhibitors of CYP3A4 (eg human immunodeficiency virus (HIV) protease inhibitors like indinavir, nelfinavir, ritonavir, atazanavir, lopinavir, amprenavir and saquinavir; macrolide/ketolide antibiotics like clarithromycin, telithromycin; antimycotic agents like itraconazole and ketoconazole [topical formulations will be allowed]; nefazodone)
  • moderate and strong inhibitors of cytochrome P450 isoenzyme 2C8 (CYP2C8) (eg gemfibrozil, montelukast, trimethoprim, glitazones)
• Women of childbearing potential, pregnant or lactating women;
• Positive results for hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), human immune deficiency virus antibodies (anti-HIV 1+2);
• Serum potassium level ≥ 5.5 mmol/L;
• Serum sodium level ≤ 130 mmol/L;

For participants with renal impairment

• Acute renal failure;
• Acute nephritis;
• Any organ transplant;
• Failure of any other major organ system other than the kidney;
• Diastolic blood pressure (DBP) > 100 mmHg and/or systolic blood pressure (SBP) > 180 mmHg (at the pre-study examination; readings taken at the end of the dosing interval of antihypertensive medication, if any);
• Heart rate below 45 or above 110 BPM at screening visit;
• Hemoglobin < 8 g/dL;
• Serum albumin < 30 g/L;
• Severe cerebrovascular or cardiac disorders, eg myocardial infarction less than 6 months prior to dosing, congestive heart failure of New York Heart Association (NYHA) grade III or IV, decompensated heart failure, severe arrhythmia requiring antiarrhythmic treatment;

For healthy participants

• A history of relevant diseases of vital organs, of the central nervous system or other organs;
• Systolic blood pressure below 100 mmHg or above 145 mmHg;
• Diastolic blood pressure above 95 mmHg;
• Heart rate below 45 or above 95 BPM at screening visit;
• Clinically relevant deviations of the screened laboratory parameters in clinical chemistry, hematology, or urinalysis from reference range;
• Relevant deviation from the normal range in the clinical examination as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal renal function; Healthy participants with creatinine clearance (CLCR) >80 mL/min received single oral dose of 10 mg BAY94-8862 as an IR tablet under fasting conditions.	Drug: Finerenone (BAY94-8862); 10 mg BAY94-8862 immediate release (IR) tablet, administered orally
Experimental: Mild renal impairment; Participants with CLCR 50-80 mL/min received single oral dose of 10 mg BAY94-8862 as an IR tablet under fasting conditions.	Drug: Finerenone (BAY94-8862); 10 mg BAY94-8862 immediate release (IR) tablet, administered orally
Experimental: Moderate renal impairment; Participants with CLCR 30-<50 mL/min received single oral dose of 10 mg BAY94-8862 as an IR tablet under fasting conditions.	Drug: Finerenone (BAY94-8862); 10 mg BAY94-8862 immediate release (IR) tablet, administered orally
Experimental: Severe renal impairment; Participants with CLCR <30 mL/min received single oral dose of 10 mg BAY94-8862 as an IR tablet under fasting conditions.	Drug: Finerenone (BAY94-8862); 10 mg BAY94-8862 immediate release (IR) tablet, administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration vs time curve from zero to infinity for total (bound and unbound) drug after single dose administration of BAY94-8862 (AUC)	AUC for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Maximum total (bound and unbound) drug concentration in plasma after single dose administration of BAY94-8862 (Cmax)	Cmax for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
AUC for unbound drug (AUCu)	AUCu for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Cmax for unbound drug (Cmax,u)	Cmax,u BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
AUC divided by dose per kg body weight (AUCnorm)	AUCnorm for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
AUCnorm for unbound drug (AUCu,norm)	AUCu, norm for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Cmax divided by dose per body weight (Cmax,norm)	Cmax, norm for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Cmax,norm for unbound drug (Cmax,u,norm)	Cmax,u,norm for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma renin activity (PRA)	Change from baseline in plasma renin activity	Prior to dosing and 12 hours post-dose
Plasma angiotensin II	Change from baseline in plasma angiotensin II	Prior to dosing and 12 hours post-dose
Serum aldosterone	Change from baseline in serum aldosterone	Prior to dosing and 12 hours post-dose
Plasminogen activator inhibitor-1 (PAI-1)	Change from baseline in PAI-1	Prior to dosing and 12 hours post-dose
Urinary volume	Change in volume of urine excreted	Prior to dosing up to 24 hours post-dose
Urinary creatinine	Change in urine creatinine concentrations	Prior to dosing up to 24 hours post-dose
Urinary electrolytes	Change in urinary electrolytes	Prior to dosing up to 24 hours post-dose
Half-life associated with the terminal slope (t½)	t½ for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Fraction unbound (fu)	fu for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	1 hour and 6 hours post-dose
AUC divided by dose (AUC/D)	AUC/D for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
AUC from time 0 to the last data point (AUC(0-tlast))	AUC(0-tlast) for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Cmax divided by dose (Cmax/D)	Cmax/D for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Time to reach Cmax (tmax)	Time to reach Cmax (in case of two identical Cmax values, the first tmax was to be used) for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Mean residence time (MRT)	MRT for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Total body clearance of drug calculated after extravascular administration (CL/F)	CL/F for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Total body clearance of unbound drug from plasma calculated after oral administration (apparent oral unbound clearance) (CLu/F)	CLu/F for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Apparent volume of distribution during terminal phase after extravascular administration (Vz/F)	Vz/F for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Amount excreted into urine from 0 to 96 h (end of urine sampling) after study drug administration (AE,ur)	AE,ur for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Percent amount excreted into urine from 0 to 96 h (end of urine sampling) after study drug administration (%AE,ur)	%AE,ur for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Renal body clearance of drug (CLR)	CLR of BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Number of participants with adverse events		Approximately 5 weeks

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Heinig R, Kimmeskamp-Kirschbaum N, Halabi A, Lentini S. Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone (BAY 94-8862) in Individuals With Renal Impairment. Clin Pharmacol Drug Dev. 2016 Nov;5(6):488-501. doi: 10.1002/cpdd.263. Epub 2016 Jul 18.

Helpful Links

• Click here to find results for studies related to Bayer products.

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2010
• Primary Completion (Actual): May 5, 2011
• Study Completion (Actual): January 27, 2012

Study Registration Dates

• First Submitted: May 27, 2021
• First Submitted That Met QC Criteria: May 27, 2021
• First Posted (Actual): June 1, 2021

Study Record Updates

• Last Update Posted (Actual): January 28, 2022
• Last Update Submitted That Met QC Criteria: January 27, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: 14509; 2010-022321-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No