A Single-Radiolabeled Dose Mass Balance Study To Investigate The Absorption, Metabolism, And Excretion Of [14C] Palbociclib (PD-0332991) In Healthy Male Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01756768
First received: December 20, 2012
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

This will be an open-label, single-center study to evaluate the mass-balance and pharmacokinetics of PD-0332991 in approximately 6 healthy male subjects receiving a single oral 125 mg dose of PD-0332991 containing approximately 100 microcuries of [14C]-PD-0332991. Subjects will be checked in to the research unit from approximately 12 hours prior to dosing and remain in house until greater than 90% of the administered radioactivity is collected from bodily excreta or until less than 1% of the administered radioactivity is recovered from excreta on consecutive days. This study will investigate the extent of involvement of the renal and hepatic systems in the elimination of PD-0332991 and will seek to identify the compound's major metabolites.


Condition Intervention Phase
Healthy
Radiation: [14C]-PD-0332991
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Phase One Open-Label Single-Radiolabeled Dose Study To Investigate The Absorption, Metabolism, And Excretion Of [14C] PD-0332991 In Healthy Male Volunteers

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of PD-0332991 [ Time Frame: 0-192 hrs ] [ 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).

  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PD-0332991 [ Time Frame: 0-192hrs ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  • Maximum Observed Plasma Concentration (Cmax) of PD-0332991 [ Time Frame: 1-24hrs ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991 [ Time Frame: 1-24hrs ] [ Designated as safety issue: No ]
  • Plasma Decay Half-Life (t1/2) of PD-0332991 [ Time Frame: 0-192hrs ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Apparent Oral Clearance (CL/F) of PD-0332991 [ Time Frame: 0-192hrs ] [ 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 (Vz/F) of PD-0332991 [ Time Frame: 0-192hrs ] [ Designated as safety issue: No ]
    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.

  • Cumulative radioactivity recovery in urine. [ Time Frame: 0-192hrs ] [ Designated as safety issue: No ]
    Cumulative radioactivity recovered in urine is the percent of the administered radioactive dose that is observed in the cumulative urine samples.

  • Cumulative radioactivity recovery in feces. [ Time Frame: 0-192hrs ] [ Designated as safety issue: No ]
    Cumulative radioactivity recovered in fecal is the percent of the administered radioactive dose that is observed in the cumulative fecal samples.


Secondary Outcome Measures:
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of PF-05089326. [ Time Frame: 0-192hrs ] [ 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).

  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05089326. [ Time Frame: 0-192hrs ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  • Maximum Observed Plasma Concentration (Cmax) of PF-05089326. [ Time Frame: 0-192hrs ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05089326. [ Time Frame: 0-192hrs ] [ Designated as safety issue: No ]
  • Plasma Decay Half-Life (t1/2) of PF-05089326. [ Time Frame: 0-192hrs ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of radioactivity in plasma. [ Time Frame: 0-192hrs ] [ 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).

  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of radioactivity in plasma. [ Time Frame: 0-192hrs ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  • Maximum Observed Concentration (Cmax) of radioactivity in plasma. [ Time Frame: 0-192hrs ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Concentration (Tmax) of radioactivity in plasma. [ Time Frame: 0-192hrs ] [ Designated as safety issue: No ]
  • Plasma Decay Half-Life (t1/2) of radioactivity in plasma. [ Time Frame: 0-192hrs ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Apparent Oral Clearance (CL/F) of radioactivity in plasma. [ Time Frame: 0-192hrs ] [ 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 (Vz/F) of radioactivity in plasma. [ Time Frame: 0-192 hrs ] [ Designated as safety issue: No ]
    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.


Enrollment: 6
Study Start Date: January 2013
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Radio-labeled Dose Arm Radiation: [14C]-PD-0332991
A single 125 mg oral dose of PD-0332991 containing approximately 100 microcurie of [14C]-PD-0332991.

  Eligibility

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

Inclusion Criteria:

  • A Healthy Male Volunteer between 18 and 55 years of age inclusive
  • A Body Mass Index (BMI) of 17.5 to 30.5 kg/m2 and a total body weight >50kg
  • A signed informed consent document

Exclusion Criteria:

  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular,hepatic,psychiatric, neurologic, or allergic disease.
  • A positive urine drug or urine cotinine screen.
  • Concurrent use of herbal or prescription medications or treatment with an investigational drug within 30 days or 5 half-lives preceding first dose of study medication.
  • Subjects whose occupation requires exposure to radiation or monitoring of radiation exposure.
  • Subjects with a history of irregular bowel movements (eg, regular episodes of diarrhea or constipation, irritable bowel syndrome (IBS) or lactose intolerance).
  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: NCT01756768

Locations
United States, Washington
Pfizer Investigational Site
Tacoma, Washington, United States, 98418
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: NCT01756768     History of Changes
Other Study ID Numbers: A5481011
Study First Received: December 20, 2012
Last Updated: December 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Phase 1
Mass Balance study
Radio-labeled dose
PD-0332991

ClinicalTrials.gov processed this record on October 01, 2014