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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Insmed Incorporated
- Enrollment
- 30
- Locations
- 3
- Primary Endpoint
- Area Under the Concentration Time Curve (AUC)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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.
Arms & Interventions
Cohort 4: Brensocatib
Participants with severe hepatic impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions.
Intervention: Brensocatib (Drug)
Cohort 1: Brensocatib
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.
Intervention: Brensocatib (Drug)
Cohort 2: Brensocatib
Participants with mild hepatic impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions.
Intervention: Brensocatib (Drug)
Cohort 3: Brensocatib
Participants with moderate hepatic impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions.
Intervention: Brensocatib (Drug)
Outcomes
Primary Outcomes
Area Under the Concentration Time Curve (AUC)
Time Frame: Pre-dose and at multiple timepoints post-dose on Days 1 to 9
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.
Secondary Outcomes
- 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))