Clinical trial NCT03432884: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Phase 1
pharmacokinetics
safety
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2018-02-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Part A: Single Group Part B: Crossover
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part A: Incidence of treatment-emergent adverse events (safety and tolerability)
timeFrame: Up to 8 days
measure: Part B: Corrected QT interval [QTc]
timeFrame: Up to 2 days
Secondary outcomes:
measure: Part A: PK Parameters
timeFrame: Up to 3 days
measure: Part B: Heart Rate (HR)
timeFrame: Up to 2 days
measure: Part B: PR Intervals
timeFrame: Up to 2 days
measure: Part B: QRS Intervals
timeFrame: Up to 2 days
measure: Part B: PK Parameters
timeFrame: Up to 2 days
measure: Part B: Incidence of treatment-emergent adverse events (safety and tolerability)
timeFrame: Up to 16 days
Other outcomes:
Locations:
city: Secaucus
country: United States
facility: Frontage Clinical Services, Inc.
state: New Jersey
Study officials:
affiliation: BeiGene
name: William Novotny, MD
role: STUDY_DIRECTOR
References:
citation: Mu S, Darpo B, Tang Z, Novotny W, Tawashi M, Xue H, Willett M, Lin L, Sahasranaman S, Ou YC. No QTc Prolongation With Zanubrutinib: Results of Concentration-QTc Analysis From a Thorough QT Study in Healthy Subjects. Clin Transl Sci. 2020 Sep;13(5):923-931. doi: 10.1111/cts.12779. Epub 2020 Apr 8.