Relative Bioavailability Of Palbociclib (PD-0332991) Under Fed And Fasted Conditions

Study Overview
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Brief Summary
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A relative bioavailability study of commercial palbociclib free base hard capsules to the isethionate salt palbociclib capsules ( used in Phase 1 and 2 studies) under different fasting conditions.

Official Title
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A Phase 1, Open-label 6 Sequence 3 Period Crossover Study of Palbociclib (PD- 0332991) in Healthy Volunteers to Estimate the Relative Bioavailability of Palbociclib Formulations

Conditions
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Healthy

Intervention / Treatment
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* Drug: palbociclib isethionate (phase 1 and 2 studies)
* Drug: palbociclib isethionate (phase 1 and 2 studies)
* Drug: palbociclib commercial free base capsule


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 has been informed of all pertinent aspects of the study. 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.

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: Palbociclib given to healthy volunteers<br> | Drug: palbociclib isethionate (phase 1 and 2 studies)<br>* 125 mg palbociclib isethionate salt under overnight fasting conditions<br>Drug: palbociclib isethionate (phase 1 and 2 studies)<br>* 125 mg palbociclib isethionate salt under minimal fasting conditions (1 hr before palbociclib administration and 2 hrs post dose)<br>Drug: palbociclib commercial free base capsule<br>* 125 mg palbociclib commercial free base capsule under fed conditions ( moderate fat meal)<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). | 7 days | 
| Maximum Observed Plasma Concentration (Cmax) |  | 7 days | 

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) | 7 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. | 7 days | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 7 days | 
| 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. | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bioavailability, bioequivalence, AUC, Cmax