Dacomitinib (PF-00299804) Pharmacokinetics In Chinese Healthy Volunteers

Study Overview
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Brief Summary
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As part of the global clinical development program for Dacomitinib, studies are planned in cancer patients in China. An assessment of Dacomitinib pharmacokinetics in Chinese subjects, as required by the Chinese Health Authorities, is therefore warranted. The single 45 mg oral dose pharmacokinetics of Dacomitinib will be characterized.

Detailed Description
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To evaluate the pharmacokinetics of Dacomitinib in Chinese healthy volunteers.

Official Title
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A Phase 1 Open-label Study To Characterize The Pharmacokinetics Of A Single 45 Mg Oral Dose Of Dacomitinib (Pf-00299804) In Healthy Chinese Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Dacomitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Chinese volunteers (individuals currently residing in mainland China, who were born in China, and whose parents are both of Chinese descent). Healthy male and/or female (of non-childbearing potential) subjects between the ages of 18 and 45 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 19.0 to 24.0 kg/m2; and a total body weight should be 50 kg (110 lbs). Exclusion Criteria: Evidence or history of clinically significant dermatologic, 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). Any condition possibly affecting drug absorption (eg, gastrectomy). Drug dependency, a positive urine drug screen and/or alcohol dependency. Use of tobacco- or nicotine- containing products (or a positive urine cotinine test). History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for men (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 or biologic within the last 3 months (or as determined by the local requirement) or 5 half-lives preceding the first dose of study medication, whichever is longer.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dacomitinib<br> | Drug: Dacomitinib<br>* A single 45 mg oral dose of Dacomitinib will be administered under fasted conditions to healthy Chinese volunteers<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Dacomitinib |  | predose, 1, 2 ,4, 6, 8, 12, 24, 48 ,72 ,96, 120, 144, 168, 192, 216, 240 ,264 hours post-dose | 
| Maximum Observed Plasma Concentration (Cmax) of Dacomitinib |  | predose, 1, 2 ,4, 6, 8, 12, 24, 48 ,72 ,96, 120, 144, 168, 192, 216, 240 ,264 hours post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]of Dacomitinib | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) | predose, 1, 2 ,4, 6, 8, 12, 24, 48 ,72 ,96, 120, 144, 168, 192, 216, 240 ,264 hours post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)of Dacomitinib |  | predose, 1, 2 ,4, 6, 8, 12, 24, 48 ,72 ,96, 120, 144, 168, 192, 216, 240 ,264 hours post-dose | 
| Apparent Volume of Distribution (Vz/F)of Dacomitinib | 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. | predose, 1, 2 ,4, 6, 8, 12, 24, 48 ,72 ,96, 120, 144, 168, 192, 216, 240 ,264 hours post-dose | 
| Plasma Decay Half-Life (t1/2)of Dacomitinib | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | predose, 1, 2 ,4, 6, 8, 12, 24, 48 ,72 ,96, 120, 144, 168, 192, 216, 240 ,264 hours post-dose | 
| Apparent Oral Clearance (CL/F)of Dacomitinib | 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. | predose, 1, 2 ,4, 6, 8, 12, 24, 48 ,72 ,96, 120, 144, 168, 192, 216, 240 ,264 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05199265 |  | predose, 1, 2 ,4, 6, 8, 12, 24, 48 ,72 ,96, 120, 144, 168, 192, 216, 240 ,264 hours post-dose | 
| Maximum Observed Plasma Concentration (Cmax) of PF-05199265 |  | predose, 1, 2 ,4, 6, 8, 12, 24, 48 ,72 ,96, 120, 144, 168, 192, 216, 240 ,264 hours post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)of PF-05199265 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | predose, 1, 2 ,4, 6, 8, 12, 24, 48 ,72 ,96, 120, 144, 168, 192, 216, 240 ,264 hours post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]of PF-05199265 | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) | predose, 1, 2 ,4, 6, 8, 12, 24, 48 ,72 ,96, 120, 144, 168, 192, 216, 240 ,264 hours post-dose | 
| Plasma Decay Half-Life (t1/2)of PF-05199265 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | predose, 1, 2 ,4, 6, 8, 12, 24, 48 ,72 ,96, 120, 144, 168, 192, 216, 240 ,264 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dacomitinib, PF299804, pharmacokinetics, Chinese, healthy