A Drug Interaction Study Between Bosutinib And Aprepitant In Healthy Volunteers

An Open-Label, Randomized, 2-Period Crossover Study To Evaluate The Effect Of A Single Dose Of Aprepitant, A Moderate CYP3A Inhibitor On Bosutinib Administered Orally To Healthy Subjects

This is an open label, randomized, single dose, one cohort, two sequence, two period crossover study in healthy subjects. The primary objective of the study is to evaluate the effect of a single oral dose of aprepitant on the pharmacokinetic (PK) profile of a single oral dose of bosutinib in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: bosutinib or bosutinib + aprepitant

• Study Type: Interventional
• Enrollment (Actual): 20
• 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: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and/or female subjects with an informed consent document signed and dated by the subject.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease
• 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 .
• Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of study medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Healthy volunteers; Healthy volunteers taking a single dose of bosutinib and a single dose of bosutinib plus aprepitant in random order	Drug: bosutinib or bosutinib + aprepitant; Single dose of bosutinib (500 mg) or single dose of bosutinib (500 mg) and aprepitant (125 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the Concentration-Time Curve (AUC)	AUC is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption.	96 hours
Maximum Observed Plasma Concentration (Cmax)	Cmax is the peak concentration.	96 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)	96 hours
Time to Reach Maximum Observed Plasma Concentration (Tmax)	Tmax is measure how fast a drug is absorbed	96 hours
Plasma Decay Half-Life (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	96 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.	96 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.	96 hours

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Hsyu PH, Pignataro DS, Matschke K. Effect of aprepitant, a moderate CYP3A4 inhibitor, on bosutinib exposure in healthy subjects. Eur J Clin Pharmacol. 2017 Jan;73(1):49-56. doi: 10.1007/s00228-016-2108-z. 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: February 6, 2014
• First Submitted That Met QC Criteria: February 6, 2014
• First Posted (ESTIMATE): February 10, 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; healthy volunteers; drug interaction; bosutinib; aprepitant; chronic myelogenous leukemia
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Neurokinin-1 Receptor Antagonists; Aprepitant
• Other Study ID Numbers: B1871041