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

NCT04454424 | Completed Phase 1 FDA Drug

• 1 other identifier: 20331
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

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.

Conditions

Endometriosis Related Pain; Overactive Bladder; Diabetic Neuropathic Pain; Refractory or Unexplained Chronic Cough

Keywords

Pharmacokinetics; Safety; Tolerability; Specific population; Subjects with hepatic impairment

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• 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

• Cmax,md,u after multiple dose of BAY1817080

  From day 6 to day 13

Study Arms (5)

Arm A: Child-Pugh A

EXPERIMENTAL

Participants with mildly impaired hepatic function (Child-Pugh A)

Drug: BAY1817080; Drug: Midazolam

Arm B: Child-Pugh B

EXPERIMENTAL

Participants with moderately impaired hepatic function (Child-Pugh B)

Drug: BAY1817080; Drug: Midazolam

Arm C: Child-Pugh C

EXPERIMENTAL

Participants with severely impaired hepatic function (Child-Pugh C)

Drug: BAY1817080; Drug: Midazolam

Arm D: Normal hepatic (Matched A and B)

EXPERIMENTAL

Participants with normal hepatic function matched to Arm A and B

Drug: BAY1817080; Drug: Midazolam

Arm E: Normal hepatic (Matched to C)

EXPERIMENTAL

Participants with normal hepatic function matched to Arm C

Drug: BAY1817080; Drug: Midazolam

Interventions

BAY1817080 DRUG

Study intervention BAY1817080 will be administered orally with tablet(s).

Arm A: Child-Pugh A; Arm B: Child-Pugh B; Arm C: Child-Pugh C; Arm D: Normal hepatic (Matched A and B); Arm E: Normal hepatic (Matched to C)

Midazolam DRUG

Midazolam will be administered intravenously with dose of 0.1 mg on Day 1.

Arm A: Child-Pugh A; Arm B: Child-Pugh B; Arm C: Child-Pugh C; Arm D: Normal hepatic (Matched A and B); Arm E: Normal hepatic (Matched to C)

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead

Study Sites (2)

Clinical Pharmacology of Miami, LLC

Miami, Florida, 33014, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32806, United States

Location

Related 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.

MeSH Terms

Conditions

Urinary Bladder, Overactive

Interventions

Midazolam

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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: June 29, 2020
• First Posted: July 1, 2020
• Study Start: July 23, 2020
• Primary Completion: June 24, 2021
• Study Completion: December 15, 2021
• Last Updated: January 20, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)