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

Phase 1
Completed
Conditions
Healthy
Interventions
Radiation: [14C]-PD-0332991
Registration Number
NCT01756768
Lead Sponsor
Pfizer
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
6
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Radio-labeled Dose Arm[14C]-PD-0332991-
Primary Outcome Measures
NameTimeMethod
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-03329911-24hrs
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of PD-03329910-192 hrs

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-03329910-192hrs

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

Cumulative radioactivity recovery in urine.0-192hrs

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.0-192hrs

Cumulative radioactivity recovered in fecal is the percent of the administered radioactive dose that is observed in the cumulative fecal samples.

Maximum Observed Plasma Concentration (Cmax) of PD-03329911-24hrs
Plasma Decay Half-Life (t1/2) of PD-03329910-192hrs

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Apparent Volume of Distribution (Vz/F) of PD-03329910-192hrs

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.

Apparent Oral Clearance (CL/F) of PD-03329910-192hrs

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.

Secondary Outcome Measures
NameTimeMethod
Time to Reach Maximum Observed Concentration (Tmax) of radioactivity in plasma.0-192hrs
Maximum Observed Plasma Concentration (Cmax) of PF-05089326.0-192hrs
Apparent Volume of Distribution (Vz/F) of radioactivity in plasma.0-192 hrs

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.

Maximum Observed Concentration (Cmax) of radioactivity in plasma.0-192hrs
Apparent Oral Clearance (CL/F) of radioactivity in plasma.0-192hrs

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.

Plasma Decay Half-Life (t1/2) of PF-05089326.0-192hrs

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.0-192hrs

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.0-192hrs

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of PF-05089326.0-192hrs

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-05089326.0-192hrs

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05089326.0-192hrs
Plasma Decay Half-Life (t1/2) of radioactivity in plasma.0-192hrs

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Trial Locations

Locations (1)

Pfizer Investigational Site

🇺🇸

Tacoma, Washington, United States

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