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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Oral Drug Formulation of PD-0332991; Drug: Intravenous Formulation of PD-0332991

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottinghamshire
    • NOttingham, Nottinghamshire, United Kingdom, NG11 6JS
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy male or female of non-childbearing potential between the ages of 18 and 55 years of age.
2. 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:

1. Any condition which could possibly affect drug absorption.
2. Pregnancy or actively nursing females, or females of childbearing potential.
3. A positive urine drug screen.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Fixed Sequence Crossover Arm; 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; Treatment A consists of a single 125 mg oral dose of PD-0332991.; Drug: Intravenous Formulation of PD-0332991; Treatment B consists of a 1000 mL intravenous infusion of 50 mg of PD-0332991 administered over 4 hours at a constant rate.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: February 27, 2013
• First Submitted That Met QC Criteria: February 27, 2013
• First Posted (Estimate): March 1, 2013

Study Record Updates

• Last Update Posted (Estimate): December 17, 2013
• Last Update Submitted That Met QC Criteria: December 16, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: PD-0332991; Absolute Bioavailability Study
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Palbociclib
• Other Study ID Numbers: A5481015; QBR115052