Drug Drug Interaction Study Of Crizotinib With Esomeprazole.

Study Overview
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Brief Summary
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This is an open-label, randomized, cross-over, single dose study in healthy volunteers to evaluate the potential effect of esomeprazole, a proton pump inhibitor, on the pharmacokinetics of crizotinib. Each subject enrolled will receive two single oral doses of crioztinib with or without esomeprazole separated by a washout period of at least 14 days.

Official Title
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A Phase 1, Open Label, Single Dose, Randomized, Cross-Over Study To Estimate The Effect Of Esomeprazole On The Pharmacokinetics Of Crizotinib In Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: crizotinib
* Drug: esomeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female of non childbearing potential subjects between the ages of 18 and 55 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG or clinical laboratory tests). Body Mass Index (BMI) of 17.5 to 30.5 kg/m^2; and a total body weight >50 kg (110 lbs). 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 time of dosing). Any condition possibly affecting drug absorption (eg, gastrectomy). A positive urine drug screen. History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening. Treatment with an investigational drug within 30 days (or as determined by the local requirement, whichever is longer) or 5 half lives preceding the first dose of study medication. Screening supine blood pressure >= 140 mm Hg (systolic) or >=90 mm Hg (diastolic), on a single measurement (confirmed by a single repeat, if necessary) following at least 5 minutes of rest. Screening 12 lead ECG demonstrating QTc >450 or a QRS interval >120 msec at Screening. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc or QRS values should be used to determine the subject's eligibility. Pregnant or nursing females; females of childbearing potential, including those with tubal ligation. 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. Herbal supplements and hormone replacement therapy must be discontinued 28 days prior to the first dose of study medication. As an exception, acetaminophen/paracetamol may be used at doses of =< 1 g/day. Limited use of non prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. A positive serology for Hepatitis B or Hepatitis C.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: crizotinib/crizotinib+esomeprazole crossover<br>Each subject in this study will receive two treatments (A and B) separated by at least 14 days of washout period. Treatment A is a 250 mg single oral dose of crizotinib administered in a fasted state as 1x 250 mg Formulated Capsule. Treatment B consists of 40 mg daily esomeprazole dose from Day 1 to Day 5 and a 250 mg single oral dose of crizotinib administered in a fasted state as 1x 250 mg Formulated Capsule on Day 5. | Drug: crizotinib<br>* Each subject in Treatment A will receive a 250 mg single oral dose of crizotinib administered in a fasted state as 1x 250 mg Formulated Capsule on Day 1 and each subject in Treatment B will receive a 250 mg single oral dose of crizotinib administered in a fasted state as 1x 250 mg Formulated Capsule on Day 5<br>Drug: esomeprazole<br>* Each subject in Treatment B will receive 40 mg daily dose of esomeprazole from Day 1 to Day 5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma AUCinf [area under the plasma concentration-time profile from time 0 to infinite time] for crizotinib |  | 2 months | 
| Plasma Cmax [maximum observed concentration] for crizotinib |  | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma AUClast [area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration] for crizotinib |  | 2 months | 
| Plasma Tmax [time for maximum observed concentration] for crizotinib |  | 2 months | 
| Plasma t1/2 [terminal half-life] for crizotinib |  | 2 months | 
| Plasma CL/F [apparent oral clearance] for crizotinib |  | 2 months | 
| Plasma Vz/F [apparent volume of distribution] for crizotinib |  | 2 months | 
| Plasma AUClast for metabolite (PF-06260182) if appropriate |  | 2 months | 
| crizotinib/metabolite AUClast ratio if appropriate |  | 2 months | 
| Plasma AUCinf for metabolite (PF-06260182) if appropriate |  | 2 months | 
| crizotinib/metabolite AUCinf ratio if appropriate |  | 2 months | 
| Plasma Cmax for metabolite (PF-06260182) if appropriate |  | 2 months | 
| crizotinib/metabolite Cmax ratio if appropriate |  | 2 months | 
| Plasma Tmax for metabolite (PF-06260182) if appropriate |  | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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crizotinib, pharmacokinetics, esomeprazole, proton pump inhibitor, drug drug interaction, healthy volunteers