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

• Sponsor: BeiGene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03432884
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 3
• Actual Duration (Months): 2.7
• Patients Per Site Per Month: 15

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: BGB-3111; Drug: Placebo; Drug: Moxifloxacin	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Part A: Single Group Part B: CrossoverPart A: Single Group Part B: Crossover
• Masking: Double (Participant, 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
• Primary Purpose: Basic Science
• 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
• Actual Study Start Date: Jan 25, 2018
• Actual Primary Completion Date: Apr 16, 2018
• Actual Study Completion Date: Apr 16, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

2. 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

1. Part A: PK Parameters [Up to 3 days]

   Plasma concentrations of zanubrutinib to evaluate protocol specified PK parameters

2. 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)

3. 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

4. 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

5. Part B: PK Parameters [Up to 2 days]

   Plasma concentrations of zanubrutinib to evaluate protocol specified PK parameters

6. Part B: Incidence of treatment-emergent adverse events (safety and tolerability) [Up to 16 days]

   Incidence of treatment-emergent adverse events reported for zanubrutinib

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Frontage Clinical Services, Inc.	Secaucus	New Jersey	United States	07094

Sponsors and Collaborators

• BeiGene

Investigators

• Study Director: William Novotny, MD, BeiGene

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: BeiGene
• ClinicalTrials.gov Identifier: NCT03432884
• Other Study ID Numbers: BGB-3111-106
• First Posted: Feb 14, 2018
• Last Update Posted: Apr 24, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by BeiGene: Phase 1; pharmacokinetics; safety
• Additional relevant MeSH terms: Moxifloxacin; Zanubrutinib

Study Results

No Results Posted as of Apr 24, 2020