A Phase 1, Open-Label, Single Dose Parallel-Group Study of Brensocatib Following a Single Oral Administration in Subjects With or Without Renal Impairment
Overview
- Phase
- Phase 1
- Intervention
- Brensocatib
- Conditions
- Renal Impairment
- Sponsor
- Insmed Incorporated
- Enrollment
- 28
- Locations
- 3
- Primary Endpoint
- Area Under the Plasma Concentration Time Curve (AUC) of Brensocatib
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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):
Arms & Interventions
Cohort 1 (Mild Impairment): Brensocatib
Participants with mild renal impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions.
Intervention: Brensocatib
Cohort 2 (Moderate Impairment): Brensocatib
Participants with moderate renal impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions.
Intervention: Brensocatib
Cohort 3 (Severe Impairment): Brensocatib
Participants with severe renal impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions.
Intervention: Brensocatib
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.
Intervention: Brensocatib
Outcomes
Primary Outcomes
Area Under the Plasma Concentration Time Curve (AUC) of Brensocatib
Time Frame: Pre-dose and at multiple timepoints post-dose on Days 1 to 14
Pharmacokinetics of brensocatib following a single dose will be assessed in participants with renal impairment and in healthy participants.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Brensocatib
Time Frame: Pre-dose and at multiple timepoints post-dose on Days 1 to 14
Maximum Observed Plasma Concentration (Cmax) of Brensocatib
Time Frame: Pre-dose and at multiple timepoints post-dose on Days 1 to 14
Number of Participants who Experienced at Least one Adverse Event (AE)
Time Frame: Up to Day 14
Determination of the safety and tolerability of a single dose of brensocatib in participants with impaired renal function and in healthy participants.