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
- Conditions
- Healthy Volunteers
- Interventions
- Registration Number
- NCT03432884
- Lead Sponsor
- BeiGene
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part A: Placebo Placebo - Part B: BGB-3111, Placebo, and Moxifloxicin BGB-3111 - Part B: BGB-3111, Placebo, and Moxifloxicin Placebo - Part A: BGB-3111 BGB-3111 - Part B: BGB-3111, Placebo, and Moxifloxicin Moxifloxacin -
- Primary Outcome Measures
Name Time Method Part A: Incidence of treatment-emergent adverse events (safety and tolerability) Up to 8 days Incidence of treatment-emergent adverse events reported for zanubrutinib compared with placebo
Part B: Corrected QT interval [QTc] Up to 2 days Evaluate the effects of single doses of zanubrutinib on the corrected QT interval \[QTc\] using the Fridericia correction \[QTcF\]) compared with placebo
- Secondary Outcome Measures
Name Time Method Part B: Incidence of treatment-emergent adverse events (safety and tolerability) Up to 16 days Incidence of treatment-emergent adverse events reported for zanubrutinib
Part B: PK Parameters Up to 2 days Plasma concentrations of zanubrutinib to evaluate protocol specified PK parameters
Part A: PK Parameters Up to 3 days Plasma concentrations of zanubrutinib to evaluate protocol specified PK parameters
Part B: Heart Rate (HR) Up to 2 days Evaluate the effects of a single dose of zanubrutinib and a single supratherapeutic dose of zanubrutinib on heart rate (HR)
Part B: PR Intervals Up to 2 days Evaluate the effects of a single dose of zanubrutinib and a single supratherapeutic dose of zanubrutinib on PR
Part B: QRS Intervals Up to 2 days Evaluate the effects of a single dose of zanubrutinib and a single supratherapeutic dose of zanubrutinib on QRS Intervals
Trial Locations
- Locations (1)
Frontage Clinical Services, Inc.
🇺🇸Secaucus, New Jersey, United States