Clinical trial NCT05355935: A Study to Investigate the Effects of Brensocatib on QT Interval in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Keywords: Brensocatib
INS1007
Lead sponsor: Insmed Incorporated
Sponsor class: INDUSTRY
First posted: 2022-05-02
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: Up to Day 7
measure: Part 2: Placebo- and Baseline-Corrected QTcF (ΔΔQTcF)
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 to 4 in each period
Secondary outcomes:
measure: Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Brensocatib
timeFrame: 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
measure: Parts 1 and 2: Time to Maximum Observed Plasma Concentration (Tmax) of Brensocatib
timeFrame: 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
measure: Parts 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Time of Last Quantifiable Concentration (AUCtlast) of Brensocatib
timeFrame: 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
measure: Parts 1 and 2: AUC From Time Zero Extrapolated to Infinity (AUC∞) of Brensocatib
timeFrame: 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
measure: Parts 1 and 2: Elimination Half-Life (t1/2) of Brensocatib
timeFrame: 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
measure: Parts 1 and 2: Total Clearance of Brensocatib Following Extravascular Administration (CL/F)
timeFrame: 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
measure: Parts 1 and 2: Volume of Distribution of Brensocatib Following Extravascular Administration (Vz/F)
timeFrame: 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
measure: Parts 2: Change From Baseline in QTcF (ΔQTcF) Interval
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 to 4 in each period
measure: Part 2: Number of Participants With Categorical Outliers for ECG Parameters: HR, PR, QRS, and QTcF
timeFrame: Pre-dose and at multiple timepoints post-dose on Days 1 to 4 in each period
measure: Part 2: Number of Participants who Experienced at least one TEAE
timeFrame: 7 days after the last dose (up to 35 days)
Other outcomes:
Locations:
city: Madison
country: United States
facility: USA001
state: Wisconsin
Study officials:
References: