A Pharmacokinetic Study to Assess Drug-drug Interaction Between Zanubrutinib and a Cocktail of Substrates in Healthy Subjects

An Open-label, Fixed-Sequence Study in Healthy Male Subjects to Assess the Drug Interaction Potential of Multiple Doses of Zanubrutinib With a Drug "Cocktail" Representative for CYP3A4, CYP2C9, CYP2C19, P-gP and BCRP Substrates

This study is designed to evaluate the safety and pharmacokinetic interaction of effects of multiple doses of zanubrutinib with a "Cocktail" of five probe drugs for cytochrome P450 (CYP) 3A, CYP2C9, CYP2C19, P-glycoprotein and breast cancer resistance protein (BCRP) in healthy subjects

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: BGB-3111 and Drug Cocktail

• Study Type: Interventional
• Enrollment (Actual): 18
• 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 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria: All Groups

• Male subjects in good health as determined by past medical history, physical examination, vital signs, ECG and laboratory tests at screening.
• Subjects must have a body mass index (BMI) between 18 and 32 kg/m2.
• Male subjects must agree to a highly effective method of birth control from screening until at least 90 days after the last dose of study drug.

Exclusion Criteria:

• Subjects 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 2 years prior to Check-In.
• Alcohol consumption of >21 units per week.
• A positive urine drug screen and/or positive alcohol breath test at Screening and/or 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.
• History of blood donation of 56 days prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.

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: Single Arm: BGB-3111 + Drug Cocktail; BGB-3111 and Drug Cocktail (midazolam, warfarin, omeprazole, digoxin and rosuvastatin)	Drug: BGB-3111 and Drug Cocktail; BGB-3111 and Drug Cocktail (midazolam, warfarin, omeprazole, digoxin and rosuvastatin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameters of probe drugs (warfarin, midazolam, digoxin, rosuvastatin, and omeprazole) derived from the plasma concentration time profile before and after oral administration of zanubrutinib	AUC from time 0 to the last quantifiable concentration (AUC0-t)	Days 1-20
PK parameters of probe drugs (warfarin, midazolam, digoxin, rosuvastatin, and omeprazole) derived from the plasma concentration time profile before and after oral administration of zanubrutinib	AUC from time 0 to infinity (AUC0 ∞; calculated as appropriate and allowed by the available data)	Days 1-20
PK parameters of probe drugs (warfarin, midazolam, digoxin, rosuvastatin, and omeprazole) derived from the plasma concentration time profile before and after oral administration of zanubrutinib	Maximum observed plasma concentration (Cmax)	Days 1-20
PK parameters of probe drugs (warfarin, midazolam, digoxin, rosuvastatin, and omeprazole) derived from the plasma concentration time profile before and after oral administration of zanubrutinib	Time of the maximum observed plasma concentration (Tmax)	Days 1-20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events as a measure of safety and tolerability.	An adverse event is an unfavorable and unintended sign (including an abnormal laboratory finding, an abnormal electrocardiogram), symptom or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.	up to 26 days

Collaborators and Investigators

• Sponsor: BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2018
• Primary Completion (Actual): June 7, 2018
• Study Completion (Actual): July 2, 2018

Study Registration Dates

• First Submitted: May 24, 2018
• First Submitted That Met QC Criteria: June 7, 2018
• First Posted (Actual): June 19, 2018

Study Record Updates

• Last Update Posted (Actual): November 4, 2019
• Last Update Submitted That Met QC Criteria: November 1, 2019
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Healthy subjects
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Zanubrutinib
• Other Study ID Numbers: BGB-3111-108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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