Relative Bioavailability of Zanubrutinib Tablets Compared to Capsules and Effects of Food on the Pharmacokinetics of the Tablet in Healthy Adults

Study Overview
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Brief Summary
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Study to assess the relative bioavailability of zanubrutinib tablets compared to capsules and to evaluate the effects of food on the pharmacokinetics (PK) of the zanubrutinib tablet.

Official Title
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A Single-dose, Open-label, Randomized, Crossover Study in Healthy Adult Subjects to Assess the Relative Bioavailability of a Zanubrutinib Tablet Compared to Zanubrutinib Capsules and to Evaluate the Effects of Food on the Pharmacokinetics of the Zanubrutinib Tablet

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Zanubrutinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index between 18.0 and 32.0 kg/m^2, inclusive In good health, determined by no clinically significant findings from medical history, 12-lead ECGs, vital signs measurements, and clinical laboratory evaluations as assessed by the investigator or designee Female participants of non-childbearing potential only Exclusion Criteria: Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator or designee Evidence of any infections (bacterial, viral, fungal, parasitic) within 4 weeks prior to the first dose of study drug, as determined by the investigator or designee History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator or designee History or presence of an abnormal ECG prior to the first dose of the study drug that, in the opinion of the investigator or designee, is clinically significant Use or intent to use prescription medications within 14 days prior to dosing or nonprescription medications/products/supplements within 7 days prior to check-in Use of tobacco or nicotine containing products within 3 months 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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All

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose Cohort<br>Zanubrutinib will be administered as a single low dose of treatment (tablet) or reference (capsule) on separate occasions across several treatment sequences | Drug: Zanubrutinib<br>* Administered orally as a tablet or capsule<br>* Other names: Brukinsa;|
| Experimental: High Dose Cohort<br>Zanubrutinib will be administered as a single high dose of treatment (tablet) or reference (capsule) on separate occasions across several treatment sequences | Drug: Zanubrutinib<br>* Administered orally as a tablet or capsule<br>* Other names: Brukinsa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) |  | Predose and up to 48 hours postdose up to Day 7 | 
| Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0-t) |  | Predose and up to 48 hours postdose up to Day 7 | 
| Maximum observed plasma concentration (Cmax) |  | Predose and up to 48 hours postdose up to Day 7 | 
| Time of the maximum observed plasma concentration (Tmax) |  | Predose and up to 48 hours postdose up to Day 7 | 
| Apparent terminal elimination half-life (t1/2) |  | Predose and up to 48 hours postdose up to Day 7 | 
| Apparent volume of distribution (Vz/F) |  | Predose and up to 48 hours postdose up to Day 7 | 
| Rate of decrease of concentration in the terminal phase (λz) |  | Predose and up to 48 hours postdose up to Day 7 | 
| Apparent oral clearance (CL/F) |  | Predose and up to 48 hours postdose up to Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) |  | Up to approximately 6 months | 
| Number of participants with clinically significant laboratory values | Laboratory values are based on hematology, clinical chemistry, and urinalysis test results | Up to approximately 6 months | 
| Number of participants with clinically significant electrocardiogram (ECG) results |  | Up to approximately 6 months | 
| Number of participants with clinically significant vital sign measurements | Vital sign measurements include supine blood pressure, supine pulse rate, respiratory rate, and oral body temperature | Up to approximately 6 months |