Evaluation Of The Potential Effect That The Administration Of Food Or Antacid Medication May Have In The Oral Absorption Of Dacomitinib (PF-00299804)

Study Overview
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Brief Summary
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Evaluation of the potential effect that the administration of food or antacid medication may have in the oral absorption of dacomitinib relative to the administration of dacomitinib in absence of food or antacid medication

Official Title
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Phase 1 Three Period Crossover Study To Evaluate The Effect Of Food And Antacids On The Pharmacokinetics, Safety & Tolerability Of PF-299,804 In Healthy Volunteers Who Have Received PF-299,804

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: dacomitinib fasted
* Drug: dacomitinib fed
* Drug: dacomitinib+antacid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects including males between the ages of 18 and 55 years. Females of non childbearing potential . Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs). An informed consent document signed and dated by the subject. Exclusion Criteria: Any condition possibly affecting drug absorption (eg, gastrectomy). A positive urine drug screen. Treatment with an investigational drug within 30 days (or as determined by the local requirement) or the appropriate time based on the elimination characteristics of the study medication.

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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fasted<br>Dacomitinib administered under fasted conditions | Drug: dacomitinib fasted<br>* Overnight fasted subjects will receive a single 45 mg dose of dacomitinib<br>|
| Experimental: Fed<br>Dacomitinib administered under fed conditions | Drug: dacomitinib fed<br>* Subjects will receive a single 45 mg dose of dacomitinib with a high calorie high fat meal<br>|
| Experimental: Antacid<br>Dacomitinib administered under antacid treatment | Drug: dacomitinib+antacid<br>* Subjects will receive a single 45 mg dose of dacomitinib when there are treated with rabeprazole<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 Extrapolated Infinite Time [AUC (0 - 8)] | AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8). For dacomitinib and PF-05199265 | 2 weeks | 
| Maximum Observed Plasma Concentration (Cmax) | For dacomitinib and PF-05199265 | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t).For dacomitinib and PF-05199265 | 2 weeks | 
| Area under the Concentration-Time Curve (AUC) | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. For dacomitinib and PF-05199265 | 3 days | 
| 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. For dacomitinib | 2 weeks | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | For dacomitinib and PF-05199265 | 2 weeks | 
| 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. For dacomitinib | 2 weeks | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. For dacomitinib | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dacomitinib, PF-00299804, fed, fasted, antacid, relative Bioavailability