A Study of the Safety, Pharmacokinetics, and Pharmacodynamics of INS1007 in Healthy Japanese and Caucasian Participants

Study Overview
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Brief Summary
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The primary purpose of Part A of this study is to compare, in a single dose and multiple doses the safety, tolerability, and pharmacokinetics (PK) profile administered in Japanese and Caucasian participants and of Part B of the study is to assess the food effect of a single dose of INS1007 administered in Japanese and Caucasian participants.

Official Title
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A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses and the Open-Label Food Effect of a Single Dose of INS1007 in Healthy Japanese and Caucasian Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: INS1007
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Japanese participants: Participant is of Japanese descent as evidenced by verbal confirmation of familial heritage (a participant must have all four grandparents born in Japan). Participants must have lived less than 10 years outside of Japan. For Caucasian participants: Participants must be of Caucasian descent, as evidenced by verbal confirmation that all four grandparents are Caucasian. Healthy, based on pre-study medical evaluation (medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory evaluations) by the PI or designee. Exclusion Criteria: Have clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s) as determined by the PI or designee. Have had serious, opportunistic, or chronic/recurring infection within 6 months prior to Screening. Examples may include, but are not limited to, infections requiring intravenous (IV) antibiotics, hospitalization, or prolonged (>14 day) anti-infective treatment. Have a history of multiple or severe allergies, or an anaphylactic reaction, to prescription or non-prescription drugs or food. Have a positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody, or human immunodeficiency virus (HIV) antigen or antibody at the Screening Visit.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Cohort 1 (Dose 1)<br>Japanese and Caucasian participants will receive INS1007 at Dose 1 or matching placebo, orally, once on Day 1, and Day 4 through Day 30 in Part A under fasted conditions. | Drug: INS1007<br>* Oral tablets.<br>* Other names: Brensocatib;Drug: Placebo<br>* Oral tablets.<br>|
| Experimental: Part A: Cohort 2 (Dose 2)<br>Japanese and Caucasian participants will receive INS1007 at Dose 2 or matching placebo, orally, once on Day 1, and Day 4 through Day 30 in Part A under fasted conditions. | Drug: INS1007<br>* Oral tablets.<br>* Other names: Brensocatib;Drug: Placebo<br>* Oral tablets.<br>|
| Experimental: Part A: Cohort 3 (Dose 3)<br>Japanese and Caucasian participants will receive INS1007 at Dose 3 or matching placebo, orally, up to Day 30 in Part A under fasted conditions. Enrollment will commence in this cohort once the safety and tolerability data in Cohort 2 is deemed acceptable by the principal investigator (PI) and the Sponsor's medical monitor. | Drug: INS1007<br>* Oral tablets.<br>* Other names: Brensocatib;Drug: Placebo<br>* Oral tablets.<br>|
| Experimental: Part B: Treatment Sequence 1<br>Japanese and Caucasian participants will receive INS1007 at the dose established in Part A after a high-fat and high-calorie breakfast on Day 1 followed by a dose established in Part A on Day 8 under fasted conditions in Part B of the study. | Drug: INS1007<br>* Oral tablets.<br>* Other names: Brensocatib;|
| Experimental: Part B: Treatment Sequence 2<br>Japanese and Caucasian participants will receive INS1007 at the dose established in Part A under fasted conditions on Day 1 followed by dose established in Part A on Day 8 after a high-fat and high-calorie breakfast in Part B of the study. | Drug: INS1007<br>* Oral tablets.<br>* Other names: Brensocatib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts A and B: Number of Participants Who Experienced at Least One Adverse Event (AE) | Determination and comparison of the safety and tolerability of INS1007 following single and multiple dose administration in Japanese and Caucasian participants. | Up to Day 61 in Part A and up to Day 11 in Part B | 
| Parts A and B: Area Under the Plasma Concentration-time Curve (AUC) of INS1007 | Comparison of the pharmacokinetics of single and multiple doses of INS1007 in Japanese and Caucasian participants. | Part A: Predose and at multiple time points postdose up to Day 33; Part B: Predose and at multiple time points postdose up to Day 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Pharmacodynamic Activity Based on Concentration of Biomarkers in Blood | Pharmacodynamic activity based on concentration of biomarkers cathepsin G (Cat G), proteinase 3 (PR3), neutrophil elastase (NE), and absolute neutrophil in blood will be assessed. | Up to Day 61 |