A Study to Investigate the Effects of Brensocatib on QT Interval in Healthy Participants
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| 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:
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:
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:
Drug: Moxifloxacin
Oral tablet.
Drug: Placebo
Oral tablet.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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)]
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | USA001 | Madison | Wisconsin | United States | 53704 |
Sponsors and Collaborators
- Insmed Incorporated
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- INS1007-104