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

Pfizer32 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Healthy Participants

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for Bosutinib

AUCinf was calculated as \[AUClast+(Clast\*/kel)\], where AUClast is the area under the plasma concentration-time profile from time 0 to the time of the Clast, Clast is the last quantifiable concentration, Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. The geometric coefficient of variation was reported as percentage