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

Study Overview
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Brief Summary
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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.

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

Conditions
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Healthy

Intervention / Treatment
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* Radiation: [14C]-PD-0332991


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radio-labeled Dose Arm<br> | Radiation: [14C]-PD-0332991<br>* A single 125 mg oral dose of PD-0332991 containing approximately 100 microcurie of [14C]-PD-0332991.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Mass Balance study, Radio-labeled dose, PD-0332991