A Two-Part Phase 1 Study to Investigate the Safety and Tolerability of Supratherapeutic Dose of Zanubrutinib and Effect of Zanubrutinib on Cardiac Repolarization in Healthy Subjects

Study Overview
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Brief Summary
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A Two-Part Phase 1 Study to Investigate A) Safety and Tolerability of Supratherapeutic dose of Zanubrutinib (BGB-3111) and B) Effect of Zanubrutinib on Cardiac Repolarization in Healthy Subjects

Detailed Description
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This is a Two-Part Phase 1 Study. Part A: This is a randomized, placebo-controlled, double blind, single dose study to evaluate the safety and tolerability of a single oral supratherapeutic dose of zanubrutinib in eight (8) subjects. Part B: This is a randomized, placebo and positive-controlled, double-blind, 4-way crossover study being conducted in about 28 subjects to investigate the effect of a single therapeutic dose of zanubrutinib, a supratherapeutic dose of zanubrutinib and placebo on cardiac repolarization. Open-label Moxifloxacin (400 mg), a fluoroquinolone broad spectrum antibiotic will be used as a positive control.

Official Title
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A Two-Part Study Consisting of a Randomized, Placebo-Controlled, Single Dose Safety and Tolerability Study (Part A) Evaluating a Supratherapeutic Dose of Zanubrutinib Followed by a Randomized, Placebo- and Positive-Controlled, Crossover Study (Part B) to Evaluate the Effect of Zanubrutinib on Cardiac Repolarization in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: BGB-3111
* Drug: Placebo
* Drug: Moxifloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects Body mass index (BMI) 18 - 33 kg/m2, inclusive. In good general health as assessed by the Investigator. Females of non-child bearing potential. Males without a vasectomy will agree to use required barrier contraception, and will agree to not donate sperm from the time of the first dose of BGB-3111 until ≥ 90 days after the last dose of BGB-3111. Able to comprehend and willing to sign consent. Exclusion Criteria: All subjects Subjects with a clinically relevant history or presence of any clinically significant disease. Personal or known family history of congenital or acquired long QT syndrome or cardiovascular disease. Women of child-bearing potential. History of alcoholism or drug/chemical abuse within 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Part A: Single Group Part B: Crossover
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: BGB-3111<br> | Drug: BGB-3111<br>* Subjects will receive BGB-3111<br>|
| Placebo Comparator: Part A: Placebo<br> | Drug: Placebo<br>* Subjects will receive Placebo<br>|
| Experimental: Part B: BGB-3111, Placebo, and Moxifloxicin<br> | Drug: BGB-3111<br>* Subjects will receive BGB-3111<br>Drug: Placebo<br>* Subjects will receive Placebo<br>Drug: Moxifloxacin<br>* Subjects will receive Moxifloxicin<br>* Other names: Avelox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Incidence of treatment-emergent adverse events (safety and tolerability) | Incidence of treatment-emergent adverse events reported for zanubrutinib compared with placebo | Up to 8 days | 
| Part B: Corrected QT interval [QTc] | Evaluate the effects of single doses of zanubrutinib on the corrected QT interval [QTc] using the Fridericia correction [QTcF]) compared with placebo | Up to 2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: PK Parameters | Plasma concentrations of zanubrutinib to evaluate protocol specified PK parameters | Up to 3 days | 
| Part B: Heart Rate (HR) | Evaluate the effects of a single dose of zanubrutinib and a single supratherapeutic dose of zanubrutinib on heart rate (HR) | Up to 2 days | 
| Part B: PR Intervals | Evaluate the effects of a single dose of zanubrutinib and a single supratherapeutic dose of zanubrutinib on PR | Up to 2 days | 
| Part B: QRS Intervals | Evaluate the effects of a single dose of zanubrutinib and a single supratherapeutic dose of zanubrutinib on QRS Intervals | Up to 2 days | 
| Part B: PK Parameters | Plasma concentrations of zanubrutinib to evaluate protocol specified PK parameters | Up to 2 days | 
| Part B: Incidence of treatment-emergent adverse events (safety and tolerability) | Incidence of treatment-emergent adverse events reported for zanubrutinib | Up to 16 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, pharmacokinetics, safety