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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Treatment Dose 1 | Experimental | Participants (in a 3:1 ratio) will receive a single oral dose of brensocatib Dose 1 or placebo, once on Day 1. |
|
| Part 1: Treatment Dose 2 | Experimental | Participants (in a 3:1 ratio) will receive a single oral dose of brensocatib Dose 2 or placebo, once on Day 1. |
|
| Part 2 | Experimental | Participants will be randomized to 1 of 4 treatment sequences (ABCD, BDAC, CADB, DCBA). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Brensocatib | Drug | Oral tablet. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| USA001 | Madison | Wisconsin | 53704 | United States |
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| ID | Term |
|---|---|
| C000619932 | brensocatib |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
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| Moxifloxacin | Drug | Oral tablet. |
|
| Placebo | Drug | Oral tablet. |
|
| 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) |
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |