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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01802476
First received: February 27, 2013
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: Oral Drug Formulation of PD-0332991
Drug: Intravenous Formulation of PD-0332991
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: 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

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Dose-Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] [ Time Frame: 0 to 144 hours ] [ Designated as safety issue: No ]
    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).

  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] [ Time Frame: 0 to 144 hours ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 0 to 144 hours ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  • Dose-Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 0 to 144 hours ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) divided by the administered dose.

  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0 to 144 hours ] [ Designated as safety issue: No ]
  • Dose-Normalized Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0 to 144 hours ] [ Designated as safety issue: No ]
    The maximum observed plasma concentration divided by the administered dose.

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0 to 144 hours ] [ Designated as safety issue: No ]
  • Plasma Decay Half-Life (t1/2) [ Time Frame: 0 to 144 hours ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Systemic Clearance (CL) [ Time Frame: 0 to 144 hours ] [ Designated as safety issue: No ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body following an intravenous dose.

  • Apparent Oral Clearance (CL/F) [ Time Frame: 0 to 144 hours ] [ Designated as safety issue: No ]
    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.

  • Apparent Volume of Distribution after an Oral Dose (Vz/F) [ Time Frame: 0 to 144 hours ] [ Designated as safety issue: No ]
  • Volume of Distribution at Steady State after an IV Infusion (Vss) [ Time Frame: 0 to 144 hours ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: May 2013
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01802476

Locations
United Kingdom
Pfizer Investigational Site
NOttingham, Nottinghamshire, United Kingdom, NG11 6JS
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01802476     History of Changes
Other Study ID Numbers: A5481015, QBR115052
Study First Received: February 27, 2013
Last Updated: December 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
PD-0332991
Absolute Bioavailability Study

ClinicalTrials.gov processed this record on September 18, 2014