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

NCT04908436 | Completed Phase 1

• 2 other identifiers: 145092010-022321-16
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Worsening Chronic Heart Failure; Chronic Kidney Disease

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (21)

• Plasma renin activity (PRA)

  Prior to dosing and 12 hours post-dose

• Plasma angiotensin II

  Prior to dosing and 12 hours post-dose

• Serum aldosterone

  Prior to dosing and 12 hours post-dose

• Plasminogen activator inhibitor-1 (PAI-1)

  Prior to dosing and 12 hours post-dose

• Urinary volume

  Prior to dosing up to 24 hours post-dose

Study Arms (4)

Normal renal function

EXPERIMENTAL

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)

Mild renal impairment

EXPERIMENTAL

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)

Moderate renal impairment

EXPERIMENTAL

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)

Severe renal impairment

EXPERIMENTAL

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)

Interventions

Finerenone (BAY94-8862) DRUG

10 mg BAY94-8862 immediate release (IR) tablet, administered orally

Mild renal impairment; Moderate renal impairment; Normal renal function; Severe renal impairment

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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);
• 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;

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

Unknown Facility

Kiel, Schleswig-Holstein, 24105, Germany

Location

Related Publications (1)

• 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.

  PMID: 27431783 RESULT

Related Links

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

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

finerenone

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2021
• First Posted: June 1, 2021
• Study Start: October 27, 2010
• Primary Completion: May 5, 2011
• Study Completion: January 27, 2012
• Last Updated: January 28, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)