A Study to Evaluate the Pharmacokinetics (PK) and Safety of a Single Dose of Brensocatib in Participants With Normal Hepatic Function and Participants With Hepatic Impairment

Hepatic Impairment Clinical Trial

Official title:

An Open-label, Phase 1 Study to Evaluate the Pharmacokinetics and Safety of a Single Dose of Brensocatib in Subjects With Normal Hepatic Function and Subjects With Hepatic Impairment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05517525
• Other study ID #: INS1007-105
• Status: Completed
• Phase: Phase 1
• Start date: October 4, 2022
• Est. completion date: June 1, 2023

Study information

• Verified date: July 2023
• Source: Insmed Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of the study is to compare the PK of a single dose of brensocatib in participants with hepatic impairment to that in matched healthy control participants with normal hepatic function.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 1, 2023
• Est. primary completion date: June 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Has body mass index (BMI) between 18.0 and 35.0 kilogram per square meter (kg/m^2)

Inclusion Criteria for Participants With Hepatic Impairment:

• Clinical diagnosis of chronic hepatic disease, as documented in their medical history of underlying hepatic insufficiency with features of cirrhosis and no acute episodes of illness within 30 days prior to screening, and no significant change in disease status from screening to check-in.

• Hepatic impairment will be classified using the Child-Pugh criteria

• A stable medication regimen, defined as not starting new drug(s) or changing dosage(s) within 30 days prior to study drug administration. Concomitant medications must be approved by the investigator and medical monitor.

Inclusion Criteria for Healthy Matched Control Participants With Normal Hepatic Function:

• In good health, determined by no clinically significant findings from medical history, clinical laboratory evaluations, vital signs measurements, 12-lead electrocardiogram (ECG), and physical examination at screening or check-in, as assessed by the investigator (or designee).

• Matched to hepatically impaired participants in age (±10 years), sex, and BMI (±20%).

Exclusion Criteria:

• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed; cholecystectomy will not be allowed).

• Positive human immunodeficiency virus (HIV) test

• Administration of a coronavirus disease 2019 (COVID-19) vaccine in the past 30 days prior to dosing.

• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days prior to dosing.

• Use of moderate to strong CYP3A4 inducers or inhibitors within 14 days prior to check-in.

• Have previously completed or withdrawn from this study or any other study investigating brensocatib, and have previously received the IMP.

Exclusion Criteria for Participants With Hepatic Impairment:

• Positive urine drug screen at screening or check-in, unless the result is due to a prescribed medication.

• History of significant immunologic impairment such as transplantation.

• Hepatic encephalopathy Grade =2 using Child-Pugh scoring.

Exclusion Criteria for Healthy Matched Control Participants with Normal Hepatic Function

• Positive urine drug screen at screening or check-in.

• Significant history or clinical manifestation of any immunologic, metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee).

• Positive hepatitis panel. Participants whose results are compatible with prior immunization are eligible at the discretion of the investigator.

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• Brensocatib
Oral tablet.

Locations

Country	Name	City	State
United States	USA003	Orlando	Florida
United States	USA002	Rialto	California
United States	USA001	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Insmed Incorporated

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Concentration Time Curve (AUC)	Comparison of the pharmacokinetics of a single dose of brensocatib in participants with hepatic impairment to that in matched healthy control participants with normal hepatic function.	Pre-dose and at multiple timepoints post-dose on Days 1 to 9
Secondary	Fraction Unbound (Fu)	Assessment of the plasma protein binding of brensocatib in participants with varying degrees of hepatic function relative to matched healthy control participants with normal hepatic function.	Pre-dose and at multiple timepoints post-dose on Days 1 to 9
Secondary	Number of Participants who Experienced at Least one Adverse Event (AE)	Determination of the safety and tolerability of a single dose of brensocatib in participants with hepatic impairment.	From first dose of study drug up to follow up visit (5-7 days after discharge) or early termination (up to Day 17)