A Study to Investigate the Effects of Brensocatib on QT Interval in Healthy Participants
Phase 1
Completed
- Conditions
- Healthy Volunteer
- Interventions
- Registration Number
- NCT05355935
- Lead Sponsor
- Insmed Incorporated
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 48
Inclusion Criteria
- 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
Exclusion Criteria
- 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)
- History of chemical abuse, illicit substance, or marijuana use within 1 year prior to check-in
- Use of tobacco- or nicotine-containing products within 3 months prior to check-in
- Receipt of blood products within 2 months prior to check-in
- Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening
- Poor peripheral venous access
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part 1: Treatment Dose 1 Placebo Participants (in a 3:1 ratio) will receive a single oral dose of brensocatib Dose 1 or placebo, once on Day 1. Part 2 Placebo Participants will be randomized to 1 of 4 treatment sequences (ABCD, BDAC, CADB, DCBA). Part 1: Treatment Dose 2 Placebo Participants (in a 3:1 ratio) will receive a single oral dose of brensocatib Dose 2 or placebo, once on Day 1. Part 1: Treatment Dose 1 Brensocatib Participants (in a 3:1 ratio) will receive a single oral dose of brensocatib Dose 1 or placebo, once on Day 1. Part 2 Brensocatib Participants will be randomized to 1 of 4 treatment sequences (ABCD, BDAC, CADB, DCBA). Part 2 Moxifloxacin Participants will be randomized to 1 of 4 treatment sequences (ABCD, BDAC, CADB, DCBA). Part 1: Treatment Dose 2 Brensocatib Participants (in a 3:1 ratio) will receive a single oral dose of brensocatib Dose 2 or placebo, once on Day 1.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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: 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: 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: 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: 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 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 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 who Experienced at least one TEAE 7 days after the last dose (up to 35 days)
Trial Locations
- Locations (1)
USA001
🇺🇸Madison, Wisconsin, United States