A Study of Brensocatib Following a Single Oral Administration in Participants With or Without Renal Impairment

A Phase 1, Open-Label, Single Dose Parallel-Group Study of Brensocatib Following a Single Oral Administration in Subjects With or Without Renal Impairment

The primary purpose of the study is to determine the pharmacokinetics (PK) following a single oral dose administration of brensocatib, safety, and tolerability of brensocatib when administered to participants with impaired renal function and in healthy participants.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: Brensocatib

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • USA002
    • Tampa, Florida, United States, 33603
      • USA003
  • Texas
    • San Antonio, Texas, United States, 78215
      • USA001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Has a body mass index (BMI) 18 to 35 kilograms per square meter (kg/m^2), inclusive, and a body weight of ≥50 kg at Screening.

Inclusion Criteria (for Participants With Renal Impairment):

• Mild, moderate, or severe renal impairment as determined by estimated glomerular filtration rate (eGFR) and calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
• Renal insufficiency or other related concomitant medical conditions (e.g., hypertension, anemia) has remained stable for at least 3 months before study drug dosing.

Inclusion Criteria for Healthy Participants:

• Normal renal function as determined by eGFR and calculated using the CKD-EDI formula, or by 24-hour urine creatinine clearance (CLcr) corrected for body size.
• In good general health, as determined by medical history, clinical laboratory assessments, vital sign measurements, 12-lead electrocardiogram (ECG) results, and physical examination findings.

Exclusion Criteria:

• Positive test result for human immunodeficiency virus types 1 or 2 antibodies, hepatitis C virus antibodies, or hepatitis B surface antigen or hepatitis B core antibodies.
• History of relevant drug and/or food allergies (i.e., allergy to brensocatib or any excipients, or any significant food allergy).
• The participant has received study drug in another investigational study within 30 days of Screening.

Exclusion Criteria (for Participants With Renal Impairment):

• Has nephrotic syndrome, defined as urine dipstick 4+ for protein and plasma albumin <3.0 grams per deciliter (g/dL), and then confirmed if proteinuria >5 g/day.
• Has an extrarenal cause of renal impairment (e.g., rapidly growing, space occupying lesions, adrenal enlargement).
• Has a functioning renal transplant (participant may be included in the study if he or she had a failed renal transplant and is not taking immunosuppressants).
• Has a hemoglobin value less than 8.5 g/dL.
• Has Type 1 or Type 2 diabetes mellitus.

Exclusion Criteria (for Healthy Participants):

• Has used any prescription (excluding hormonal birth control, hormone replacement therapy, nonsteroidal anti-inflammatory drugs, or acetaminophen) or over-the-counter medications, including herbal or nutritional supplements, within 14 days before study drug dosing and throughout the study.

Note: Other inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (Mild Impairment): Brensocatib; Participants with mild renal impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions.	Drug: Brensocatib; Oral tablet; Other Names: INS1007
Experimental: Cohort 2 (Moderate Impairment): Brensocatib; Participants with moderate renal impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions.	Drug: Brensocatib; Oral tablet; Other Names: INS1007
Experimental: Cohort 3 (Severe Impairment): Brensocatib; Participants with severe renal impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions.	Drug: Brensocatib; Oral tablet; Other Names: INS1007
Experimental: Cohort 4 (Normal): Brensocatib; Healthy participants with normal renal function will receive single oral dose of brensocatib on Day 1 under fasted conditions. Healthy participants will be matched within the protocol criteria to one or more participants with renal impairment.	Drug: Brensocatib; Oral tablet; Other Names: INS1007

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration Time Curve (AUC) of Brensocatib	Pharmacokinetics of brensocatib following a single dose will be assessed in participants with renal impairment and in healthy participants.	Pre-dose and at multiple timepoints post-dose on Days 1 to 14
Maximum Observed Plasma Concentration (Cmax) of Brensocatib		Pre-dose and at multiple timepoints post-dose on Days 1 to 14
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Brensocatib		Pre-dose and at multiple timepoints post-dose on Days 1 to 14
Number of Participants who Experienced at Least one Adverse Event (AE)	Determination of the safety and tolerability of a single dose of brensocatib in participants with impaired renal function and in healthy participants.	Up to Day 14

Collaborators and Investigators

• Sponsor: Insmed Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2021
• Primary Completion (Actual): February 14, 2023
• Study Completion (Actual): February 14, 2023

Study Registration Dates

• First Submitted: December 21, 2022
• First Submitted That Met QC Criteria: December 21, 2022
• First Posted (Actual): January 6, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 17, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Brensocatib; INS1007
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: INS1007-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No