Drug Interaction Study Between Bosutinib And Dabigatran

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Dabigatran; Drug: Bosutinib

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • DeLand, Florida, United States, 32720
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dabigatran; Dabigatran 150 mg orally	Drug: Dabigatran; Dabigatran 150 mg orally
Experimental: Dabigatran + Bosutinib; Dabigatran 150 mg co-administered with Bosutinib 500 mg orally	Drug: Dabigatran; Dabigatran 150 mg orally; Drug: Bosutinib; Bosutinib 500 mg orally

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Hsyu PH, Pignataro DS, Matschke K. Effect of bosutinib on the absorption of dabigatran etexilate mesylate, a P-glycoprotein substrate, in healthy subjects. Eur J Clin Pharmacol. 2017 Jan;73(1):57-63. doi: 10.1007/s00228-016-2115-0. Epub 2016 Oct 7.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: March 31, 2014
• First Submitted That Met QC Criteria: March 31, 2014
• First Posted (Estimate): April 3, 2014

Study Record Updates

• Last Update Posted (Estimate): June 24, 2014
• Last Update Submitted That Met QC Criteria: June 23, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: pharmacokinetics; drug interaction; bosutinib; dabigatran; p-glycoprotein
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran
• Other Study ID Numbers: B1871043