Study on the Safety of BAY1817080 How it is Tolerated and the Way the Body Absorbs, Distributes and Gets Rid of the Study Drug Given to Participants With Moderate Renal Impairment and End Stage Renal Disease Requiring Dialysis Compared With Matched Participants With Normal Renal Function

An Open-label Study to Evaluate the Pharmacokinetics and Safety of BAY 1817080 in Participants With Impaired Renal Function in Comparison to Matched Controls With Normal Renal Function

BAY1817080 is currently under clinical development to treat pain related to unexplained chronic cough or chronic cough not affected by a treatment (refractory and/or unexplained chronic cough, RUCC), or a condition where the bladder is unable to hold urine normally (overactive bladder, OAB) or a condition in which tissue similar to the tissue that normally lines the inside of the womb grows outside the womb (endometriosis). Especially in elderly patients with OAB or RUCC, renal impairment is frequent. Renal impairment which co-occurs in especially in elderly patients with OAB or RUCC is a common condition in which the kidneys are not filtering the blood as well as they should. End stage renal disease (ESRD) requiring hemodialysis is a condition in which patients kidneys are no longer able to work as they should and require treatment to filter wastes from the blood. The goal of the study is to learn more about the safety of BAY1817080, how it is tolerated and the way the body absorbs, distributes and excretes the study drug given in men and women with moderate renal impairment and with those who have end stage renal disease (ESRD) requiring dialysis compared with matched participants with normal kidney function.

Study Overview

• Status: Completed
• Conditions: Overactive Bladder; Diabetic Neuropathic Pain; Endometriosis Related Pain; Refractory or Unexplained Chronic Cough
• Intervention / Treatment: Drug: BAY1817080

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami, LLC
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participant must be 18 to 79 years of age inclusive, at the time of signing the informed consent.

• For renally impaired participants:

  • Decreased renal function, as assessed based on serum creatinine collected 2 to 10 days prior to dosing and calculated according to the Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) either: Moderately impaired renal function: eGFR: 30 to 59 mL/min/1.73 m^2; or ESRD on dialysis.
  • Stable renal disease, i.e. a serum creatinine value determined 3 or more months before screening (e.g. during routine diagnostics) should not differ by more than 25% from the serum creatinine value determined at screening.

• For participants with normal renal function:

  -- Normal renal function, as assessed at screening and based on serum creatinine according to the CKD-EPI : eGFR ≥90 mL/min/1.73 m^2.

• Body mass index (BMI) within the range 18 to 38 kg/m^2 (both inclusive)
• Women of childbearing potential (WOCBP) must agree to use contraception for the duration of the study. This applies for the time period between signing of the Informed Consent Form until at least 30 days after the last dose of the study drug.
• Capable of giving signed informed consent as described in study protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

• Any relevant disease (other than those related to renal impairment for the renal impaired participants) within 4 weeks prior to study drug administration including infections and acute gastro-intestinal diseases (vomiting, diarrhea, constipation) requiring medical treatment.
• Acute renal failure or acute nephritis within the past 2 years
• Use of strong CYP3A4 and P-glycoprotein inhibitors from 2 weeks before study treatment until last day of blood sampling for pharmacokinetics after study drug administration.
• Use of CYP3A4 and P-glycoprotein inducers from 2 weeks before study treatment until last day of blood sampling for pharmacokinetics after study drug administration.
• Use of drugs which may affect absorption (e.g. loperamide, metoclopramide), and systemic administration of any broad-spectrum antibiotic within 1 week before first study drug administration, unless the drug is part of the mandatory dosing regimen for treatment of renal impairment or related conditions.
• International Normalized Ratio (INR) > 2.3.
• Indication or evidence for long QT syndrome; Participants in control group only: QT interval corrected using Fridericia's method (QTcF) > 450 msec.
• Inability to provide informed consent: Participants with psychiatric disorders.

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: Arm A: Moderately impaired renal function; Participants with moderately impaired renal function will receive multiple doses of BAY1817080.	Drug: BAY1817080; BAY1817080 will be administered orally as tablet.
Experimental: Arm B: Normal renal function matched to Arm A; Participants with normal renal function matched to Arm A will receive multiple doses of BAY1817080.	Drug: BAY1817080; BAY1817080 will be administered orally as tablet.
Experimental: Arm C: End stage renal disease on dialysis; Participants with ESRD requiring dialysis will receive single dose of BAY1817080.	Drug: BAY1817080; BAY1817080 will be administered orally as tablet.
Experimental: Arm D: Normal renal function matched to Arm C; Participants with normal renal function matched to Arm C will receive single dose of BAY1817080.	Drug: BAY1817080; BAY1817080 will be administered orally as tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCu after single dose of BAY1817080	AUCu: Area under the Curve unbound	On Day 1
Cmax,u after single dose of BAY1817080	Cmax,u: maximum observed drug concentration in measured matrix after single dose administration (unbound)	On Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with treatment emergent adverse events (TEAEs)		From dosing up to 14 days after end of treatment with study medication
AUC (0-12)md,u after multiple dose of BAY1817080	Area under the time curve from 0-12 hours at steady state for the multiple dose (unbound)	From Day 6 to Day 13
Cmax,md,u after multiple dose of BAY1817080	Cmax,md,u: Maximum observed drug concentration at steady state for multiple dose (unbound)	From Day 6 to Day 13

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2020
• Primary Completion (Actual): February 15, 2021
• Study Completion (Actual): May 6, 2021

Study Registration Dates

• First Submitted: July 10, 2020
• First Submitted That Met QC Criteria: July 10, 2020
• First Posted (Actual): July 15, 2020

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Dialysis; End stage renal disease (ESRD); Moderate renal impairment; Normal renal function
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Signs and Symptoms, Respiratory; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Cough; Urinary Bladder, Overactive; Neuralgia; Endometriosis; Chronic Cough
• Other Study ID Numbers: 20332 (UK NIHR CRN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There are no current plans to share data. Interested researchers can use www.vivli.org 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 member section of the portal.

Drug and device information, study documents

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