A Study To Establish The Equivalence Of 2 Palbociclib (PD-0332991) Formulations To The Intended Final Market Product

Study Overview
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Brief Summary
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This study is intended to establish the equivalence of 2 formulations to the intended final market product. The formulations to compare are the capsule given to patients in the phase I and II studies and the capsule that is being administered to the patients in the phase III trials. Both capsules will be compared to the intended final market capsule. The comparison will be performed looking at the pharmacokinetic parameters that define the rate and extent of absorption, those are Cmax and AUC. A statistical analysis will be performed comparing these parameters calculated after a single 125 mg dose of the 3 capsules identifying like that if there are significant differences between these 3 formulations.

Official Title
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A Phase 1, Open-Label 3 Sequence 3 Period Crossover Study Of Palbociclib (PD-0332991) In Healthy Volunteers To Establish The Bioequivalence Of The Phase 1/2 And Phase 3 Formulation To Palbociclib ICH Formulation Under Fasted Conditions

Conditions
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Healthy

Intervention / Treatment
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* Drug: palbociclib capsule: phase 1 and 2 studies
* Drug: Palbociclib capsule: phase 3 studies
* Drug: Palbociclib capsule: ICH


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 capsule: phase 1 and 2 studies<br>* 125 mg dose of palbociclib. Formulation used in phase 1 and 2 studies<br>Drug: Palbociclib capsule: phase 3 studies<br>* 125 mg dose of palbociclib. Formulation used in phase 3 studies<br>Drug: Palbociclib capsule: ICH<br>* 125 mg dose of palbociclib. Intended final market formulation<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 | 
| 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) | 7 days | 
| Area Under the Curve From Time Zero to 72 hrs [AUC (0-72)] | AUC (0-72)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 72 hrs(0-72) | 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. | 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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Bioequivalence, Cmax, AUC