The Effect of Moderate CYP3A Inducer Rifabutin on the Pharmacokinetics of Zanubrutinib in Healthy Males

A Phase 1, Open-label, Fixed-sequence Study to Investigate the Effect of the Moderate CYP3A Inducer Rifabutin on the Pharmacokinetics of Zanubrutinib in Healthy Male Subjects

The primary objective of this study was to determine the effect of the moderate cytochrome P450 3A (CYP3A) inducer rifabutin on the pharmacokinetics (PK) of zanubrutinib in healthy males.

Study Overview

• Status: Completed
• Conditions: Healthy; Male
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Rifabutin

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Covance Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

1. Males of any race, between 18 and 65 years of age, inclusive.
2. Male participants in good health as determined by past medical history, physical examination, vital signs, ECG and laboratory tests at screening
3. Must have a body mass index (BMI) between 18 and 32 kg/m^2

Key Exclusion Criteria:

1. Participants with a clinically relevant history or presence of any clinically significant disease
2. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair will be allowed)
3. History of drug or alcohol abuse within 1 year prior to check-in
4. Use or intended use of any nonprescription medications/products including vitamins, minerals, herbal/plant-derived preparations within 7 days prior to check-in
5. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result and/or a positive human immunodeficiency virus (HIV) at screening
6. Use of tobacco- or nicotine-containing products within 3 months prior to check-in
7. Use or intended use of any prescription medications/products within 14 days prior to check-in

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zanubrutinib + Rifabutin; Day 1: zanubrutinib Days 3 to 10: rifabutin Day 11: zanubrutinib and rifabutin	Drug: Zanubrutinib; Single oral dose of 320 mg; Other Names: Brukinsa; BGB-3111; Drug: Rifabutin; Oral dose of 300 mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Zanubrutinib	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
AUC From Time Zero to Infinity (AUC0-∞) of Zanubrutinib	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Maximum Observed Plasma Concentration (Cmax) of Zanubrutinib	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Time to the Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Time of the Last Quantifiable Concentration (Tlast) of Zanubrutinib	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Apparent Terminal Elimination Half-life (t1/2) of Zanubrutinib	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Apparent Oral Clearance (CL/F) of Zanubrutinib	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Apparent Volume of Distribution (Vz/F) of Zanubrutinib	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Adverse Events (AEs)	Adverse events (AEs) and serious adverse events included for summary, AEs that start during or after the first dose, or start prior to the first dose and increases in severity after the first dose, including vital signs, physical examination, electrocardiogram, and laboratory parameters	From the date of first study drug administration to 30 days after last dose (up to 3.5 months)

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Principal Investigator: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2020
• Primary Completion (Actual): November 10, 2020
• Study Completion (Actual): November 10, 2020

Study Registration Dates

• First Submitted: July 10, 2020
• First Submitted That Met QC Criteria: July 10, 2020
• First Posted (Actual): July 14, 2020

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: March 10, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Healthy volunteers; Pharmacokinetics; Phase 1
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Protein Kinase Inhibitors; Antitubercular Agents; Antibiotics, Antitubercular; Rifabutin; Zanubrutinib
• Other Study ID Numbers: BGB-3111-112

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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