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

Overactive Bladder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04454424
• Other study ID #: 20331
• Status: Completed
• Phase: Phase 1
• Start date: July 23, 2020
• Est. completion date: December 15, 2021

Study information

• Verified date: January 2023
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: December 15, 2021
• Est. primary completion date: June 24, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetic Neuropathic Pain
• Endometriosis
• Endometriosis Related Pain
• Neuralgia
• Overactive Bladder
• Urinary Bladder, Overactive

Intervention

Drug:
• BAY1817080
Study intervention BAY1817080 will be administered orally with tablet(s).
• Midazolam
Midazolam will be administered intravenously with dose of 0.1 mg on Day 1.

Locations

Country	Name	City	State
United States	Clinical Pharmacology of Miami, LLC	Miami	Florida
United States	Orlando Clinical Research Center	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUCu after single dose of BAY1817080	AUCu: Area under the Curve unbound	On day 1
Primary	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	Number of subjects with treatment-emergent adverse events		from dosing up to 14 days after end of treatment with study medication
Secondary	AUC (0-12)md,u after multiple dose of BAY1817080	AUC (0-12)md,u: Area Under the Curve from 0-12 hours at steady state for the multiple dose (unbound)	From day 6 to day 13
Secondary	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

External Links

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