A Study to Investigate the Effects of Brensocatib on QT Interval in Healthy Participants

A Two-part, Phase I, Double-blind, Placebo- and Positive-controlled Crossover Study to Investigate the Effects of Brensocatib on QT Interval in Healthy Subjects

The study has 2 Parts: The primary purpose of Part 1 is to determine the supratherapeutic dose of brensocatib to be used in Part 2 of the study.

The primary purpose of Part 2 is to assess brensocatib's potential for prolonging the QT interval.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: Brensocatib; Drug: Placebo; Drug: Moxifloxacin

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • USA001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Body mass index (BMI) between 18.0 and 32.0 kilogram per square metre (kg/m^2), inclusive, and a total body weight greater than or equal to 50 kilograms (kg)
2. Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception
3. Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions
4. Able to swallow tablets

Exclusion Criteria:

1. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator (or designee)
2. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs
3. QTcF interval >430 ms for males and >440 ms for females or QRS >120 ms
4. A history of additional risk factors for torsade de pointes (eg, heart failure, hypokalemia, or family history of long QT syndrome)
5. Positive serology test results for hepatitis B panel and hepatitis C antibody and/or reactive human immunodeficiency virus 1/2 test
6. Administration of a coronavirus disease 2019 (COVID-19) vaccine in the past 14 days prior to dosing
7. Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to dosing, unless deemed acceptable by the investigator (or designee)
8. Use or intend to use any prescription medications/products within 14 days prior to dosing, unless deemed acceptable by the investigator (or designee)
9. Use or intend to use slow-release medications/products considered to still be active within 14 days prior to check-in, unless deemed acceptable by the investigator (or designee)
10. Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to check-in, unless deemed acceptable by the investigator (or designee)
11. Use or intend to use any medications that may increase QT interval within 14 days prior to check-in
12. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days prior to dosing
13. Have previously completed or withdrawn from this study or any other study investigating brensocatib, and have previously received brensocatib
14. Alcohol consumption of >14 units per week for males and >7 units for females. One unit of alcohol equals 12 ounce (oz) (360 milliliter [mL]) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine
15. Consumption of caffeine-containing products within 48 hours prior to check-in, unless deemed acceptable by the investigator (or designee)
16. History of chemical abuse, illicit substance, or marijuana use within 1 year prior to check-in
17. Use of tobacco- or nicotine-containing products within 3 months prior to check-in
18. Receipt of blood products within 2 months prior to check-in
19. Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening
20. Poor peripheral venous access

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Treatment Dose 1; Participants (in a 3:1 ratio) will receive a single oral dose of brensocatib Dose 1 or placebo, once on Day 1.	Drug: Brensocatib; Oral tablet.; Other Names: INS1007; Drug: Placebo; Oral tablet.
Experimental: Part 1: Treatment Dose 2; Participants (in a 3:1 ratio) will receive a single oral dose of brensocatib Dose 2 or placebo, once on Day 1.	Drug: Brensocatib; Oral tablet.; Other Names: INS1007; Drug: Placebo; Oral tablet.
Experimental: Part 2; Participants will be randomized to 1 of 4 treatment sequences (ABCD, BDAC, CADB, DCBA).	Drug: Brensocatib; Oral tablet.; Other Names: INS1007; Drug: Placebo; Oral tablet.; Drug: Moxifloxacin; Oral tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1: Number of Participants who Experienced at least one Treatment-Emergent Adverse Event (TEAE) as Assessed by Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0)	Up to Day 7
Part 2: Placebo- and Baseline-Corrected QTcF (ΔΔQTcF)	Pre-dose and at multiple timepoints post-dose on Days 1 to 4 in each period

Secondary Outcome Measures

Outcome Measure	Time Frame
Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Brensocatib	Part 1: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part 2: Pre-dose and at multiple timepoints post-dose on Days 1 to 4 in each period
Parts 1 and 2: Time to Maximum Observed Plasma Concentration (Tmax) of Brensocatib	Part 1: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part 2: Pre-dose and at multiple timepoints post-dose on Days 1 to 4 in each period
Parts 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Time of Last Quantifiable Concentration (AUCtlast) of Brensocatib	Part 1: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part 2: Pre-dose and at multiple timepoints post-dose on Days 1 to 4 in each period
Parts 1 and 2: AUC From Time Zero Extrapolated to Infinity (AUC∞) of Brensocatib	Part 1: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part 2: Pre-dose and at multiple timepoints post-dose on Days 1 to 4 in each period
Parts 1 and 2: Elimination Half-Life (t1/2) of Brensocatib	Part 1: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part 2: Pre-dose and at multiple timepoints post-dose on Days 1 to 4 in each period
Parts 1 and 2: Total Clearance of Brensocatib Following Extravascular Administration (CL/F)	Part 1: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part 2: Pre-dose and at multiple timepoints post-dose on Days 1 to 4 in each period
Parts 1 and 2: Volume of Distribution of Brensocatib Following Extravascular Administration (Vz/F)	Part 1: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part 2: Pre-dose and at multiple timepoints post-dose on Days 1 to 4 in each period
Parts 2: Change From Baseline in QTcF (ΔQTcF) Interval	Pre-dose and at multiple timepoints post-dose on Days 1 to 4 in each period
Part 2: Number of Participants With Categorical Outliers for ECG Parameters: HR, PR, QRS, and QTcF	Pre-dose and at multiple timepoints post-dose on Days 1 to 4 in each period
Part 2: Number of Participants who Experienced at least one TEAE	7 days after the last dose (up to 35 days)

Collaborators and Investigators

• Sponsor: Insmed Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2022
• Primary Completion (Actual): October 7, 2022
• Study Completion (Actual): October 7, 2022

Study Registration Dates

• First Submitted: April 26, 2022
• First Submitted That Met QC Criteria: April 26, 2022
• First Posted (Actual): May 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Brensocatib; INS1007
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: INS1007-104

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