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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy, Male

Intervention / Treatment
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* Drug: Zanubrutinib
* Drug: Rifabutin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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 Key Exclusion Criteria: 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 NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Zanubrutinib + Rifabutin<br>Day 1: zanubrutinib Days 3 to 10: rifabutin Day 11: zanubrutinib and rifabutin | Drug: Zanubrutinib<br>* Single oral dose of 320 mg<br>* Other names: Brukinsa;Drug: Rifabutin<br>* Oral dose of 300 mg once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Healthy volunteers, Pharmacokinetics