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

A Phase One Open-Label Single-Radiolabeled Dose Study To Investigate The Absorption, Metabolism, And Excretion Of [14C] PD-0332991 In Healthy Male Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Radiation: [14C]-PD-0332991

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Tacoma, Washington, United States, 98418
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of PD-0332991	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).	0-192 hrs
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PD-0332991	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	0-192hrs
Maximum Observed Plasma Concentration (Cmax) of PD-0332991		1-24hrs
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991		1-24hrs
Plasma Decay Half-Life (t1/2) of PD-0332991	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	0-192hrs
Apparent Oral Clearance (CL/F) of PD-0332991	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.	0-192hrs
Apparent Volume of Distribution (Vz/F) of PD-0332991	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.	0-192hrs
Cumulative radioactivity recovery in urine.	Cumulative radioactivity recovered in urine is the percent of the administered radioactive dose that is observed in the cumulative urine samples.	0-192hrs
Cumulative radioactivity recovery in feces.	Cumulative radioactivity recovered in fecal is the percent of the administered radioactive dose that is observed in the cumulative fecal samples.	0-192hrs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of PF-05089326.	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).	0-192hrs
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05089326.	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	0-192hrs
Maximum Observed Plasma Concentration (Cmax) of PF-05089326.		0-192hrs
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05089326.		0-192hrs
Plasma Decay Half-Life (t1/2) of PF-05089326.	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	0-192hrs
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of radioactivity in plasma.	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).	0-192hrs
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of radioactivity in plasma.	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	0-192hrs
Maximum Observed Concentration (Cmax) of radioactivity in plasma.		0-192hrs
Time to Reach Maximum Observed Concentration (Tmax) of radioactivity in plasma.		0-192hrs
Plasma Decay Half-Life (t1/2) of radioactivity in plasma.	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	0-192hrs
Apparent Oral Clearance (CL/F) of radioactivity in plasma.	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.	0-192hrs
Apparent Volume of Distribution (Vz/F) of radioactivity in plasma.	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.	0-192 hrs

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: January 1, 2013
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: December 20, 2012
• First Submitted That Met QC Criteria: December 20, 2012
• First Posted (Estimate): December 27, 2012

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: Phase 1; PD-0332991; Mass Balance study; Radio-labeled dose
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Palbociclib
• Other Study ID Numbers: A5481011