A Study to Investigate Effect of Clarithromycin, a Strong CYP3A4 Inhibitor, on Brensocatib Pharmacokinetics in Healthy Participants

A Phase 1, Open-label, Fixed-sequence Study to Investigate the Effect of Clarithromycin, a Strong CYP3A4 Inhibitor, on Brensocatib Pharmacokinetics in Healthy Subjects

The primary purpose of this study is to determine the effect of clarithromycin on the single-dose pharmacokinetics (PK) of brensocatib in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Brensocatib; Drug: Clarithromycin

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Insmed Medical Information; Phone Number: 1-844-446-7633; Email: medicalinformation@insmed.com

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • USA001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Females of nonchildbearing potential and males, of any race, between 18 and 65 years of age, inclusive, without current disease.
• Body mass index between 18.0 and 32.0 kilograms per square meter (kg/m^2), inclusive, and a total body weight ≥50 kilograms (kg).

Exclusion Criteria:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee).
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator (or designee).
• 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 serology test results for hepatitis B panel or hepatitis C antibody and/or reactive human immunodeficiency virus 1/2 test.
• Participants whose results are compatible with prior immunization for hepatitis B or natural immunity may be included at the discretion of the investigator.
• Positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test at screening or check-in.
• Poor peripheral venous access. Note: Other inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Brensocatib + Clarithromycin; Participants will receive a single oral dose of brensocatib in the morning on Days 1 and 13 after an overnight fast, and oral doses of clarithromycin, twice daily (BID), with food on Days 8 to 19. On Day 13, brensocatib will be coadministered with the morning dose of clarithromycin. Clarithromycin can be taken with food, with the exception of the morning dose on the day of coadministration with brensocatib (Day 13), which will be taken after an overnight fast.

Drug: Brensocatib; Oral tablets.; Other Names: INS1007; Drug: Clarithromycin; Oral tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Curve (AUC) of Brensocatib	The effect of clarithromycin on the single dose pharmacokinetics of brensocatib will be assessed in healthy participants.	Pre-dose and at multiple timepoints post-dose on Days 1 to 8, and Days 13 to 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants who Experienced at Least one Adverse Event (AE)	Determination of the safety and tolerability of a single oral dose of brensocatib when administered alone and with clarithromycin in healthy participants.	Up to Day 27

Collaborators and Investigators

• Sponsor: Insmed Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2023
• Primary Completion (Actual): September 22, 2023
• Study Completion (Actual): September 22, 2023

Study Registration Dates

• First Submitted: July 19, 2023
• First Submitted That Met QC Criteria: July 19, 2023
• First Posted (Actual): July 28, 2023

Study Record Updates

• Last Update Posted (Actual): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Clarithromycin
• Other Study ID Numbers: INS1007-109

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No