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

Healthy Volunteer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05355935
• Other study ID #: INS1007-104
• Status: Completed
• Phase: Phase 1
• Start date: April 27, 2022
• Est. completion date: October 7, 2022

Study information

• Verified date: March 2023
• Source: Insmed Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: October 7, 2022
• Est. primary completion date: October 7, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• Brensocatib
Oral tablet.
• Moxifloxacin
Oral tablet.
• Placebo
Oral tablet.

Locations

Country	Name	City	State
United States	USA001	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Insmed Incorporated

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Part 2: Placebo- and Baseline-Corrected QTcF (??QTcF)		Pre-dose and at multiple timepoints post-dose on Days 1 to 4 in each period
Secondary	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
Secondary	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
Secondary	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
Secondary	Parts 1 and 2: AUC From Time Zero Extrapolated to Infinity (AUC8) 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
Secondary	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
Secondary	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
Secondary	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
Secondary	Parts 2: Change From Baseline in QTcF (?QTcF) Interval		Pre-dose and at multiple timepoints post-dose on Days 1 to 4 in each period
Secondary	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
Secondary	Part 2: Number of Participants who Experienced at least one TEAE		7 days after the last dose (up to 35 days)