Evaluation of the Relative Bioavailability of Bosutinib Capsules Under Fed Condition and Estimation of Food Effect on Orally Administered Bosutinib Capsule

Study Overview
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Brief Summary
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This study is intended to estimate the bioavailability of a single 100 mg bosutinib capsules relative to four 25 mg capsules under fed condition in adult healthy participants and to estimate the effect of a high-fat, high-calorie meal on the bioavailability of a single 100 mg capsule of bosutinib relative to fasted condition in adults healthy participants. The comparisons will be performed using the pharmacokinetic parameters that define the rate and extend of absorption (Cmax, AUC). Statistical analyses will be performed after the administration of a single 100 mg dose under fed condition as the Reference treatment and the four 25 mg capsules as the Test treatment for the first comparison, and after administration of a single 100 mg dose under fasted condition as the Reference treatment and the 100 mg capsule under fed condition as the Test treatment for the second comparison.

Official Title
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A PHASE 1, RANDOMIZED, OPEN-LABEL, 3-PERIOD, 4-SEQUENCE, CROSSOVER, SINGLE-DOSE STUDY TO COMPARE THE BIOAVAILABILITY OF ORALLY ADMINISTERED BOSUTINIB CAPSULES AND TO ESTIMATE THE EFFECT OF FOOD ON BOSUTINIB CAPSULE

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: Bosutinib capsule
* Drug: Bosutinib capsule
* Drug: Bosutinib
* Drug: Bosutinib capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female participants of non-childbearing potential and/or male participants must be 18 to 55 years of age, inclusive, at the time of signing the informed consent document (ICD) participants who are overtly healthy as determined by medical evaluation including a detailed medical history, complete physical examination, vital signs which include BP and pulse rate measurement, clinical laboratory tests, and electrocardiogram (ECG). Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, dermatological, or allergic disease. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy). History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg,hepatitis B surface antigen (HBcAb) or hepatitis C antibody (HCVAb). Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary: estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) <90 mL/min/1.73 m2; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level >upper limit of normal (ULN); Serum (total and direct) bilirubin level > ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is <= ULN; Amylase and lipase level > ULN.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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
Interventional Model Description: A Phase 1, open-label, randomized, single dose, 3-period, 4 sequence, crossover study in healthy participants
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment B: Bosutinib four 25 mg capsule after meal<br>Bosutinib four 25 mg capsule taken after a high-fat and high-calorie breakfast for comparison 1 | Drug: Bosutinib capsule<br>* Bosutinib four 25 mg capsule taken after a high-fat and high calorie breakfast<br>|
| Active Comparator: Treatment A: Bosutinib 100 mg capsule after meal (active comparator)<br>Bosutinib 100 mg capsule taken after a high-fat and high-calorie breakfast for comparison 1 | Drug: Bosutinib capsule<br>* Bosutinib 100 mg capsule taken after a high-fat and high calorie breakfast<br>|
| Experimental: Treatment A: Bosutinib 100 mg capsule after meal (experimental)<br>Bosutinib 100 mg capsule taken after a high-fat and high-calorie breakfast for comparison 2 | Drug: Bosutinib capsule<br>* Bosutinib 100 mg capsule taken after a high-fat and high-calorie breakfast<br>|
| Active Comparator: Treatment C: Bosutinib 100 mg capsule after fasting<br>Bosutinib 100 mg capsule taken after an overnight fast of at least 10 hours for comparison 2 | Drug: Bosutinib<br>* Bosutinib 100 mg capsule taken after an overnight fast of at least 10 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] |  | 6 days | 
| Cmax |  | 6 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) |  | 6 days | 
| Time to Cmax (Tmax) |  | 6 days | 
| Apparent Oral Clearance (CL/F) |  | 6 days | 
| Apparent Volume of Distribution (Vz/F) |  | 6 days | 
| Plasma elimination half-life (t1/2) |  | 6 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioavailability, Food Effect, Bosutinib, Maximum Observed Plasma Concentration (Cmax), Area Under the Curve (AUC)