Bioavailability of Bosutinib Administered as Capsule Contents Mixed With Applesauce or Yogurt Relative to Intact Capsules Under Fed Condition

Study Overview
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Brief Summary
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This study is intended to estimate the relative bioavailability of a single 500 mg dose of bosutinib when administered as capsule contents mixed with applesauce or yogurt to intact capsules under fed condition in adult healthy participants. The comparisons will be performed using the pharmacokinetic parameters that define the rate and extent of absorption, those are Cmax and AUC. Statistical analyses will be performed comparing these parameters calculated after administration of a single 500 mg dose with the intact capsule formulation (100 mg x 5) as the Reference treatment and the capsule contents mixed with applesauce or yogurt (100 mg x 5) as the Test treatments.

Official Title
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A PHASE 1, OPEN-LABEL, RANDOMIZED, 3-PERIOD, 6-SEQUENCE, CROSSOVER STUDY TO EVALUATE THE BIOAVAILABILITY OF BOSUTINIB ADMINISTERED AS CAPSULE CONTENTS MIXED WITH APPLESAUCE OR YOGURT RELATIVE TO INTACT CAPSULES IN HEALTHY PARTICIPANTS UNDER FED CONDITION

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: Bosutinib capsule
* Drug: Bosutinib capsule
* 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 54 years of age, inclusive, at the time of signing the informed consent document (ICD). Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol. 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. 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 levels > 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, 6-sequence, crossover study in healthy participants
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bosutinib capsule contents mixed with applesauce<br>Bosutinib capsule contents mixed with applesauce to healthy participants | Drug: Bosutinib capsule<br>* 500 mg dose of bosutinib capsule contents mixed with applesauce<br>|
| Experimental: Bosutinib capsule contents mixed with yogurt<br>Bosutinib capsule contents mixed with yogurt to healthy participants | Drug: Bosutinib capsule<br>* 500 mg dose of bosutinib capsule contents mixed with yogurt<br>|
| Active Comparator: Bosutinib intact capsules<br>Bosutinib intact capsules to healthy participants | Drug: Bosutinib capsule<br>* 500 mg dose of intact bosutinib capsules<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, bosutinib, Maximum Observed Plasma Concentration (Cmax), Area Under the Curve (AUC)