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

NCT04470908 | Completed Phase 1 Results FDA Drug

• 1 other identifier: BGB-3111-112
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy; Male

Keywords

Phase 1; Healthy volunteers; Pharmacokinetics

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (1)

• Number of Participants Experiencing Adverse Events (AEs)

  From the date of first study drug administration to 30 days after last dose (up to 3.5 months)

Study Arms (1)

Zanubrutinib + Rifabutin

EXPERIMENTAL

Day 1: zanubrutinib Days 3 to 10: rifabutin Day 11: zanubrutinib and rifabutin

Drug: Zanubrutinib; Drug: Rifabutin

Interventions

Zanubrutinib DRUG

Single oral dose of 320 mg

Also known as: BGB-3111, Brukinsa

Zanubrutinib + Rifabutin

Rifabutin DRUG

Oral dose of 300 mg once daily

Zanubrutinib + Rifabutin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Participants with a clinically relevant history or presence of any clinically significant disease
• 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)
• History of drug or alcohol abuse within 1 year prior to check-in
• Use or intended use of any nonprescription medications/products including vitamins, minerals, herbal/plant-derived preparations within 7 days prior to check-in
• A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result and/or a positive human immunodeficiency virus (HIV) at screening
• Use of tobacco- or nicotine-containing products within 3 months prior to check-in
• Use or intended use of any prescription medications/products within 14 days prior to check-in

Sponsors & Collaborators

• BeiGene: lead

Study Sites (1)

Covance Clinical Research Unit

Daytona Beach, Florida, 32117, United States

Location

Related Publications (1)

• Tariq B, Conto S, Cohen A, Sahasranaman S, Ou YC. A Phase 1, Open-Label, Fixed-Sequence, Drug-Drug Interaction Study of Zanubrutinib with Rifabutin in Healthy Volunteers. Clin Pharmacol Drug Dev. 2023 Aug;12(8):832-838. doi: 10.1002/cpdd.1250. Epub 2023 May 5.

  PMID: 37145975 DERIVED

MeSH Terms

Interventions

zanubrutinib; Rifabutin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2020
• First Posted: July 14, 2020
• Study Start: July 29, 2020
• Primary Completion: November 10, 2020
• Study Completion: November 10, 2020
• Last Updated: October 26, 2024
• Results First Posted: December 14, 2023

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

US (1)