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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: BGB-3111; Drug: Placebo; Drug: Moxifloxacin

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Secaucus, New Jersey, United States, 07094
      • Frontage Clinical Services, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part A: BGB-3111	Drug: BGB-3111; Subjects will receive BGB-3111
PLACEBO_COMPARATOR: Part A: Placebo	Drug: Placebo; Subjects will receive Placebo
EXPERIMENTAL: Part B: BGB-3111, Placebo, and Moxifloxicin	Drug: BGB-3111; Subjects will receive BGB-3111; Drug: Placebo; Subjects will receive Placebo; Drug: Moxifloxacin; Subjects will receive Moxifloxicin; Other Names: Avelox

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: BeiGene

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 25, 2018
• Primary Completion (ACTUAL): April 16, 2018
• Study Completion (ACTUAL): April 16, 2018

Study Registration Dates

• First Submitted: January 19, 2018
• First Submitted That Met QC Criteria: February 13, 2018
• First Posted (ACTUAL): February 14, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 24, 2020
• Last Update Submitted That Met QC Criteria: April 22, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: safety; pharmacokinetics; Phase 1
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Protein Kinase Inhibitors; Moxifloxacin; Zanubrutinib
• Other Study ID Numbers: BGB-3111-106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No