A Study Comparing the Plasma Drug Exposure of an Oral Dose of Palbociclib (PD-0332991) to an Intravenous Dose of Palbociclib (PD-0332991)

Study Overview
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Brief Summary
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The purpose of this study is to determine approximately what percentage of an orally administered dose of PD-0332991 is absorbed from the gastrointestinal tract into the systemic circulation. This approximation is made by comparing the plasma pharmacokinetics of a 125 mg oral dose of PD-0332991 to the plasma pharmacokinetics of a 50 mg intravenous dose of PD-0332991 administered as a 4-hour infusion.

Official Title
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A Phase 1, Single Dose, Fixed Sequence, 2-Period Cross-Over Absolute Oral Bioavailability Study In Healthy Volunteers Comparing Oral To Intravenous Administration Of PD-0332991

Conditions
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Healthy

Intervention / Treatment
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* Drug: Oral Drug Formulation of PD-0332991
* Drug: Intravenous Formulation of PD-0332991


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female of non-childbearing potential between the ages of 18 and 55 years of age. A body mass index (BMI) between 17.5 and 30.5 kg/m2, and a total body weight greater than 50kg (110 lbs) Exclusion Criteria: Any condition which could possibly affect drug absorption. Pregnancy or actively nursing females, or females of childbearing potential. A positive urine drug screen.

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 |
| --- | --- |
| Other: Fixed Sequence Crossover Arm<br>This study arm consists of a fixed sequence crossover where study subjects will receive Treatment A and following a washout of no less than 10 days will then receive Treatment B. The drug class is a CDK4/6 inhibitor. | Drug: Oral Drug Formulation of PD-0332991<br>* Treatment A consists of a single 125 mg oral dose of PD-0332991.<br>Drug: Intravenous Formulation of PD-0332991<br>* Treatment B consists of a 1000 mL intravenous infusion of 50 mg of PD-0332991 administered over 4 hours at a constant rate.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] | Dose-Normalized AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8) divided by the administered dose. It is obtained from AUC (0 - t) plus AUC (t - 8). | 0 to 144 hours | 
| 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). | 0 to 144 hours | 

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) | 0 to 144 hours | 
| Dose-Normalized 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) divided by the administered dose. | 0 to 144 hours | 
| Maximum Observed Plasma Concentration (Cmax) |  | 0 to 144 hours | 
| Dose-Normalized Maximum Observed Plasma Concentration (Cmax) | The maximum observed plasma concentration divided by the administered dose. | 0 to 144 hours | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 0 to 144 hours | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 0 to 144 hours | 
| Systemic Clearance (CL) | CL is a quantitative measure of the rate at which a drug substance is removed from the body following an intravenous dose. | 0 to 144 hours | 
| 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. | 0 to 144 hours | 
| Apparent Volume of Distribution after an Oral Dose (Vz/F) |  | 0 to 144 hours | 
| Volume of Distribution at Steady State after an IV Infusion (Vss) |  | 0 to 144 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD-0332991, Absolute Bioavailability Study