Drug Interaction Study Between Bosutinib And Dabigatran

Study Overview
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Brief Summary
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The study evaluates the effect of a single oral dose of bosutinib on the single dose pharmacokinetics of dabigatran, a p-glycoprotein substrate, in healthy subjects.

Official Title
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An Open-Label, Randomized, 2-Period Crossover Study To Evaluate The Effect Of A Single Oral Dose Of Bosutinib On The Pharmacokinetics Of Dabigatran Etexilate Mesylate Administered Orally To Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Dabigatran
* Drug: Bosutinib
* Drug: Dabigatran


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects between 21 to 55 years old and BMI between 17.5 and 30.5 kg/m2. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). Risks of bleeding including prior personal or familiar history of abnormal bleeding, hereditary or acquired coagulation or platelet disorder or abnormal coagulation test (PT/INR or PTT/aPTT greater than upper limit of normal) result at screening. Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of non-hormonal contraception as outlined in this protocol from at least 14 days prior to the first dose of study medication.

Ages Eligible for Study
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Minimum Age: 21 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dabigatran<br>Dabigatran 150 mg orally | Drug: Dabigatran<br>* Dabigatran 150 mg orally<br>|
| Experimental: Dabigatran + Bosutinib<br>Dabigatran 150 mg co-administered with Bosutinib 500 mg orally | Drug: Bosutinib<br>* Bosutinib 500 mg orally<br>Drug: Dabigatran<br>* Dabigatran 150 mg orally<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 Last Quantifiable Concentration (AUClast) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | 48 hours | 
| Maximum Observed Plasma Concentration (Cmax) | Maximum Observed Plasma Concentration | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | 48 hours | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Time to Reach Maximum Observed Plasma Concentration | 48 hours | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 48 hours | 
| Apparent Oral Clearance (CL/F) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | 48 hours | 
| Apparent Volume of Distribution (Vz/F) | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dabigatran, bosutinib, drug interaction, p-glycoprotein, pharmacokinetics