Healthy Volunteers
Conditions
Keywords
Phase 1, pharmacokinetics, safety
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.
Interventions
DRUGBGB-3111
Subjects will receive BGB-3111
DRUGPlacebo
Subjects will receive Placebo
DRUGMoxifloxacin
Subjects will receive Moxifloxicin
Sponsors
BeiGene
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Part A: zanubrutinib and placebo will be double-blind Part B: zanubrutinib and placebo will be double-blind; Moxifloxacin will be open-label
Intervention model description
Part A: Single Group Part B: Crossover
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
All subjects 1. Body mass index (BMI) 18 - 33 kg/m2, inclusive. 2. In good general health as assessed by the Investigator. 3. Females of non-child bearing potential. 4. 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. 5. Able to comprehend and willing to sign consent.
Exclusion criteria
All subjects 1. Subjects with a clinically relevant history or presence of any clinically significant disease. 2. Personal or known family history of congenital or acquired long QT syndrome or cardiovascular disease. 3. Women of child-bearing potential. 4. History of alcoholism or drug/chemical abuse within 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Part A: PK Parameters | Up to 3 days | Plasma concentrations of zanubrutinib to evaluate protocol specified PK parameters |
| 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 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) |
Countries
United States
Outcome results
None listed