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

• ClinicalTrials.gov Identifier: NCT03561298
• Recruitment Status: Completed
• First Posted: June 19, 2018
• Last Update Posted: November 4, 2019
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Healthy Subjects	Drug: BGB-3111 and Drug Cocktail	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: June 7, 2018
• Actual Primary Completion Date: June 7, 2018
• Actual Study Completion Date: July 2, 2018

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. 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 Frame: Days 1-20 ]
   AUC from time 0 to the last quantifiable concentration (AUC0-t)
2. 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 Frame: Days 1-20 ]
   AUC from time 0 to infinity (AUC0 ∞; calculated as appropriate and allowed by the available data)
3. 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 Frame: Days 1-20 ]
   Maximum observed plasma concentration (Cmax)
4. 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 Frame: Days 1-20 ]
   Time of the maximum observed plasma concentration (Tmax)

Secondary Outcome Measures :

1. Number of participants with adverse events as a measure of safety and tolerability. [ Time Frame: up to 26 days ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Florida

Covance Clinical Research Unit

Daytona Beach, Florida, United States, 32117

Sponsors and Collaborators

BeiGene

Investigators

• Study Director: William Novotny, MD; BeiGene

More Information

• Responsible Party: BeiGene
• ClinicalTrials.gov Identifier: NCT03561298
• Other Study ID Numbers: BGB-3111-108
• First Posted: June 19, 2018
• Last Update Posted: November 4, 2019
• Last Verified: October 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by BeiGene:

Pharmacokinetics; Healthy subjects

Additional relevant MeSH terms:

Zanubrutinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action