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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03432884
• Other study ID #: BGB-3111-106
• Status: Completed
• Phase: Phase 1
• Start date: January 25, 2018
• Est. completion date: April 16, 2018

Study information

• Verified date: April 2020
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 16, 2018
• Est. primary completion date: April 16, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• BGB-3111
Subjects will receive BGB-3111
• Placebo
Subjects will receive Placebo
• Moxifloxacin
Subjects will receive Moxifloxicin

Locations

Country	Name	City	State
United States	Frontage Clinical Services, Inc.	Secaucus	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 Mar 7. doi: 10.11 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Part A: PK Parameters	Plasma concentrations of zanubrutinib to evaluate protocol specified PK parameters	Up to 3 days
Secondary	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
Secondary	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
Secondary	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
Secondary	Part B: PK Parameters	Plasma concentrations of zanubrutinib to evaluate protocol specified PK parameters	Up to 2 days
Secondary	Part B: Incidence of treatment-emergent adverse events (safety and tolerability)	Incidence of treatment-emergent adverse events reported for zanubrutinib	Up to 16 days