A Study To Understand How Radiolabelled PF-04449913 Is Taken Up By The Body, Broken Down And Then Removed From The Body

Study Overview
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Brief Summary
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The study aims to understand, using radiolabelled PF-04449913, how this compound is modified by the body once it is absorbed. The study also aims to understand how much of the compound is broken down and how much leaves the body unchanged.

Official Title
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A Phase One Open-Label Single-Radiolabeled Dose Study To Investigate The Absorption, Metabolism, And Excretion Of [14C] PF-04449913 In Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: [14C] PF-04449913


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects between the ages of 18 and 55 years (inclusive):Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs). An informed consent document signed and dated by the subject. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Subjects enrolled in a previous radionucleotide study or who have received radiotherapy within 12 months prior to screening or such that total radioactivity would exceed acceptable dosimetry. A positive urine drug screen or urine cotinine test 12 lead ECG demonstrating QTc >450 or a QRS interval >120 msec msec at Screening. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc values should be used to determine the subject's eligibility. Subjects with family history of myocardial infarction, congenital long QT syndrome, torsades de pointes or clinically significant ventricular arrhythmias. Subjects should be within normal range of potassium, magnesium and calcium at screening.

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: Treatment<br> | Drug: [14C] PF-04449913<br>* Single oral dose of 100 mg PF-04449913 + 100µCi of [14C] PF-04449913<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)] | 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). | 7 days | 
| Maximum Observed Plasma Concentration (Cmax) |  | 7 days | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] for total radioactivity related to drug product | AUC (0 - 8)= Area under the plasma radioactivity 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). | 7 days | 
| Maximum Observed Plasma Concentration (Cmax) for total radioactivity related to drug product |  | 7 days | 
| Cumulative recovery of radioactivity in excreta | Total percentage of dosed radioactivity recovered in urine and feces | 7 days | 
| Radioactivity in blood | Total percentage of radioactivity in blood related to drug product | 7 days | 
| Urine PF-04449913 PK parameters | Measure of renal clearance (CLr), amount excreted unchanged in urine (Ae) and the fraction of dose excreted unchanged in urine (AE%) | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | 7 days | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 7 days | 
| Apparent Oral Clearance (CL/F) | 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. | 7 days | 
| Apparent Volume of Distribution (Vz/F) | plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PF-04449913, [14C]PF-04449913, Human ADME, Radiolabel, Mass Balance, Pharmacokinetics