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

NCT05355935 | Completed Phase 1 FDA Drug

• 1 other identifier: INS1007-104
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteer

Keywords

Brensocatib; INS1007

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (10)

• 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

Study Arms (3)

Part 1: Treatment Dose 1

EXPERIMENTAL

Participants (in a 3:1 ratio) will receive a single oral dose of brensocatib Dose 1 or placebo, once on Day 1.

Drug: Brensocatib; Drug: Placebo

Part 1: Treatment Dose 2

EXPERIMENTAL

Participants (in a 3:1 ratio) will receive a single oral dose of brensocatib Dose 2 or placebo, once on Day 1.

Drug: Brensocatib; Drug: Placebo

Part 2

EXPERIMENTAL

Participants will be randomized to 1 of 4 treatment sequences (ABCD, BDAC, CADB, DCBA).

Drug: Brensocatib; Drug: Moxifloxacin; Drug: Placebo

Interventions

Brensocatib DRUG

Oral tablet.

Also known as: INS1007

Part 1: Treatment Dose 1; Part 1: Treatment Dose 2; Part 2

Moxifloxacin DRUG

Oral tablet.

Part 2

Placebo DRUG

Oral tablet.

Part 1: Treatment Dose 1; Part 1: Treatment Dose 2; Part 2

Eligibility Criteria

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

You may qualify if:

• 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)
• Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception
• Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions
• Able to swallow tablets

You may not qualify if:

• 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
• QTcF interval \>430 ms for males and \>440 ms for females or QRS \>120 ms
• A history of additional risk factors for torsade de pointes (eg, heart failure, hypokalemia, or family history of long QT syndrome)
• Positive serology test results for hepatitis B panel and hepatitis C antibody and/or reactive human immunodeficiency virus 1/2 test
• Administration of a coronavirus disease 2019 (COVID-19) vaccine in the past 14 days prior to dosing
• 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)
• Use or intend to use any prescription medications/products within 14 days prior to dosing, unless deemed acceptable by the investigator (or designee)
• 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)
• 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)
• Use or intend to use any medications that may increase QT interval within 14 days prior to check-in
• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days prior to dosing
• Have previously completed or withdrawn from this study or any other study investigating brensocatib, and have previously received brensocatib
• 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
• Consumption of caffeine-containing products within 48 hours prior to check-in, unless deemed acceptable by the investigator (or designee)

Sponsors & Collaborators

• Insmed Incorporated: lead

Study Sites (1)

USA001

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Interventions

brensocatib; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2022
• First Posted: May 2, 2022
• Study Start: April 27, 2022
• Primary Completion: October 7, 2022
• Study Completion: October 7, 2022
• Last Updated: March 27, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)