Study on the Safety of BAY1817080, How it is Tolerated and the Way the Body Absorbs, Distributes and Gets Rid of the Study Drug in Participants With Impaired Liver Function or Normal Liver Function

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT04454424

Collaborator

(none)

Enrollment

Locations

Arms

16.8

Actual Duration (Months)

18.5

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

In this study researchers want to learn more about the safety of BAY1817080, how it is tolerated and the way the body absorbs, distributes and gets rid of the study dug given as tablet in participants with mild, moderate or severe hepatic impairment and participants with normal liver function matched for age-, gender-, weight and race.

The study will enroll 36 male and female participants in the age between 18 and 79 years. Participants with mild or moderate hepatic impairment and the matching participants will take multiple oral doses of study drug depending on the study plan. Participants with severe hepatic impairment and the matching participants will take a single oral dose of study drug during the study. Data from this study will provide researcher important information for further development of the study drug in particular on dose recommendation for patients with hepatic impairment.

Condition or Disease	Intervention/Treatment	Phase
Endometriosis Related Pain Overactive Bladder Diabetic Neuropathic Pain Refractory or Unexplained Chronic Cough	Drug: BAY1817080 Drug: Midazolam	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

37 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

An Open-label Study to Evaluate the Pharmacokinetics, Safety and Tolerability of BAY 1817080 in Participants With Impaired Hepatic Function (Classified as Child-Pugh A, B or C) in Comparison to Matched Controls With Normal Hepatic Function

Actual Study Start Date :

Jul 23, 2020

Actual Primary Completion Date :

Jun 24, 2021

Actual Study Completion Date :

Dec 15, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Child-Pugh A Participants with mildly impaired hepatic function (Child-Pugh A)	Drug: BAY1817080 Study intervention BAY1817080 will be administered orally with tablet(s). Drug: Midazolam Midazolam will be administered intravenously with dose of 0.1 mg on Day 1.
Experimental: Arm B: Child-Pugh B Participants with moderately impaired hepatic function (Child-Pugh B)	Drug: BAY1817080 Study intervention BAY1817080 will be administered orally with tablet(s). Drug: Midazolam Midazolam will be administered intravenously with dose of 0.1 mg on Day 1.
Experimental: Arm C: Child-Pugh C Participants with severely impaired hepatic function (Child-Pugh C)	Drug: BAY1817080 Study intervention BAY1817080 will be administered orally with tablet(s). Drug: Midazolam Midazolam will be administered intravenously with dose of 0.1 mg on Day 1.
Experimental: Arm D: Normal hepatic (Matched A and B) Participants with normal hepatic function matched to Arm A and B	Drug: BAY1817080 Study intervention BAY1817080 will be administered orally with tablet(s). Drug: Midazolam Midazolam will be administered intravenously with dose of 0.1 mg on Day 1.
Experimental: Arm E: Normal hepatic (Matched to C) Participants with normal hepatic function matched to Arm C	Drug: BAY1817080 Study intervention BAY1817080 will be administered orally with tablet(s). Drug: Midazolam Midazolam will be administered intravenously with dose of 0.1 mg on Day 1.

Outcome Measures

Primary Outcome Measures

AUCu after single dose of BAY1817080 [On day 1]
AUCu: Area under the Curve unbound
Cmax,u after single dose of BAY1817080 [On day 1]
Cmax,u: maximum observed drug concentration in measured matrix after single dose administration (unbound)

Secondary Outcome Measures

Number of subjects with treatment-emergent adverse events [from dosing up to 14 days after end of treatment with study medication]
AUC (0-12)md,u after multiple dose of BAY1817080 [From day 6 to day 13]
AUC (0-12)md,u: Area Under the Curve from 0-12 hours at steady state for the multiple dose (unbound)
Cmax,md,u after multiple dose of BAY1817080 [From day 6 to day 13]
Cmax,md,u: Maximum observed drug concentration at steady state for multiple dose (unbound)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 79 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participant must be 18 to 79 years of age inclusive, at the time of signing the informed consent.
Participants with a medical history of chronic (For Hepatically Impaired Participants only):
documented liver cirrhosis confirmed by histopathology, laparoscopy, fibroscan, CT, MRI or ultrasound, AND
hepatic impairment (Child-Pugh A or B or C), AND
stable liver disease, i.e. same Child-Pugh class for at least 2 months prior to screening.
Body mass index (BMI) within the range 18 to 38 kg/m^2 (both inclusive).
Male or female.
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 hepatic impairment for the hepatic impaired participants) within 4 weeks prior to study drug administration including infections and acute gastro-intestinal diseases (vomiting, diarrhea, constipation) requiring medical treatment.
Renal failure with an estimated glomerular filtration rate (eGFR) ≤ 35 mL/min, according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
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 hepatic impairment or related conditions.
Indication or evidence for long QT syndrome; Participants in control arm only: QT interval corrected using Fridericia's method (QTcF) > 450 msec.
Ascites qualitatively estimated as severe ascites by physical examination, with need of paracentesis; or a recent history of paracentesis.
Alkaline phosphatase (AP) ≥4 times the upper limit of normal (ULN).
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) in conjunction with gamma-glutamyl transpeptidase (GGT) ≥4 times the ULN (an isolated elevation of GGT above 4 times ULN will not exclude the participant).
International Normalized Ratio (INR) > 2.7.
Inability to provide informed consent: Participants with psychiatric disorders, including hepatic encephalopathy >grade 2, e.g. number connection test >80 seconds.