Characterization Of The Effect Of Food On Palbociclib (PD-0332991) Absorption

Study Overview
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Brief Summary
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This study is intended to quantify the effect of food on the extent of absorption of palbociclib. The caloric content of the food and the time of the meals with respect to palbociclib administration may influence the capacity of the body to absorb the drug. High and low calorie meals will be given to the subjects 30 minutes before palbociclib administration as 2 of the 3 conditions to compare with completely absence of food in the body when dosing (fasted).The third condition to test and compare with fasted stage will be the administration of food before and after palbociclib administration. This information will help the program to decide wether or not the presence of food when dosing palbociclib help with its absorption and to what extent it does help. Based on the collected information, a recommendation about the administration of palbociclib with food will be provided to patients.

Official Title
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A Phase 1, Open-Label 4 Sequence 4 Period Crossover Study Of Palbociclib (PD-0332991) In Healthy Volunteers To Estimate The Effect Of Food On The Bioavailability Of Palbociclib

Conditions
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Healthy

Intervention / Treatment
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* Drug: Palbociclib administered Fasted
* Drug: Palbociclib administered Fed high calorie
* Drug: Palbociclib administered Fed low calorie
* Drug: Palbociclib administered Fed moderate calorie


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects and/or female subjects of non-childbearing potential between the ages of 18 and 55 years Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease Any condition possibly affecting drug absorption Male subjects who are unwilling or unable to use a highly effective method of contraception

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Palbociclib given to healthy volunteers<br> | Drug: Palbociclib administered Fasted<br>* palbociclib given under fasting 10 hrs overnight; capsule form, 125 mg single dose<br>Drug: Palbociclib administered Fed high calorie<br>* palbociclib given right after a high fat high calorie meal; capsule form, 125 mg single dose<br>Drug: Palbociclib administered Fed low calorie<br>* palbociclib given right after a low fat low calorie meal; capsule form, 125 mg single dose<br>Drug: Palbociclib administered Fed moderate calorie<br>* palbociclib given between moderate calorie meal; capsule form, 125 mg single dose<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). | 144 hrs | 
| Maximum Observed Plasma Concentration (Cmax) |  | 144 hrs | 

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) | 144 hrs | 
| 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) | 144 hrs | 
| Area under the Concentration-Time Curve (AUC) from 0 to 72 hrs | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. | 144 hrs | 
| 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. | 144 hrs | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 144 hrs | 
| 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. | 144 hrs | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 144 hrs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Food, Bioavailability, Fasted, Fed