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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: BGB-3111 and Drug Cocktail


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm: BGB-3111 + Drug Cocktail<br>BGB-3111 and Drug Cocktail (midazolam, warfarin, omeprazole, digoxin and rosuvastatin) | Drug: BGB-3111 and Drug Cocktail<br>* BGB-3111 and Drug Cocktail (midazolam, warfarin, omeprazole, digoxin and rosuvastatin)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Healthy subjects