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

NCT05517525 | Completed Phase 1 FDA Drug

• 1 other identifier: INS1007-105
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Hepatic Impairment

Keywords

Brensocatib; INS1007

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Fraction Unbound (Fu)

  Pre-dose and at multiple timepoints post-dose on Days 1 to 9

• Number of Participants who Experienced at Least one Adverse Event (AE)

  From first dose of study drug up to follow up visit (5-7 days after discharge) or early termination (up to Day 17)

Study Arms (4)

Cohort 1: Brensocatib

EXPERIMENTAL

Healthy participants with normal hepatic function will receive single oral dose of brensocatib on Day 1 under fasted conditions. Healthy participants will be matched within the protocol criteria to one or more participants with hepatic impairment.

Drug: Brensocatib

Cohort 2: Brensocatib

EXPERIMENTAL

Participants with mild hepatic impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions.

Drug: Brensocatib

Cohort 3: Brensocatib

EXPERIMENTAL

Participants with moderate hepatic impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions.

Drug: Brensocatib

Cohort 4: Brensocatib

EXPERIMENTAL

Participants with severe hepatic impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions.

Drug: Brensocatib

Interventions

Brensocatib DRUG

Oral tablet.

Also known as: INS1007

Cohort 1: Brensocatib; Cohort 2: Brensocatib; Cohort 3: Brensocatib; Cohort 4: Brensocatib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Insmed Incorporated: lead

Study Sites (3)

USA002

Rialto, California, 92377, United States

Location

USA003

Orlando, Florida, 32809, United States

Location

USA001

San Antonio, Texas, 78215, United States

Location

Related Publications (1)

• Usansky H, Au Yeung S, Li S, Marbury T, Lawitz E, Kayali Z, Stein DS. Pharmacokinetics and Safety of a Single Dose of Brensocatib in Participants with Hepatic Impairment and Matched Participants with Normal Hepatic Functions. Clin Pharmacokinet. 2026 Jan 26. doi: 10.1007/s40262-025-01614-0. Online ahead of print.

  PMID: 41586857 DERIVED

MeSH Terms

Interventions

brensocatib

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2022
• First Posted: August 26, 2022
• Study Start: October 4, 2022
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: July 19, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)