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

Study Overview
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Brief Summary
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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.

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

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: Brensocatib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (Mild Impairment): Brensocatib<br>Participants with mild renal impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions. | Drug: Brensocatib<br>* Oral tablet<br>* Other names: INS1007;|
| Experimental: Cohort 2 (Moderate Impairment): Brensocatib<br>Participants with moderate renal impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions. | Drug: Brensocatib<br>* Oral tablet<br>* Other names: INS1007;|
| Experimental: Cohort 3 (Severe Impairment): Brensocatib<br>Participants with severe renal impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions. | Drug: Brensocatib<br>* Oral tablet<br>* Other names: INS1007;|
| Experimental: Cohort 4 (Normal): Brensocatib<br>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<br>* Oral tablet<br>* Other names: INS1007;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brensocatib, INS1007