Study to Characterize Absorption, Distribution, Metabolism and Excretion of 14C PF-06651600 and to Evaluate the Absolute Oral Bioavailability and Fraction Absorbed of PF-06651600.

Study Overview
=================
Brief Summary
-----------------
This study will investigate the absorption, distribution, metabolism and excretion (ADME) of 14C PF-06651600 and characterize plasma, fecal and urinary radioactivity and identify any metabolites, if possible, of 14C PF-06651600 in humans.

Official Title
-----------------
A PHASE 1, OPEN-LABEL, NON-RANDOMIZED, 2-PERIOD, FIXED SEQUENCE STUDY TO INVESTIGATE THE ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION OF 14C-PF-06651600 AND TO ASSESS THE ABSOLUTE BIOAVAILABILITY AND FRACTION ABSORBED OF PF-06651600 IN HEALTHY MALE PARTICIPANTS USING A 14C-MICROTRACER APPROACH

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: 14C-PF-06651600
* Drug: 14C-PF-06651600 IV
* Drug: PF-06651600


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male participants who are healthy as determined by medical evaluation including a detailed medical history, full physical examination, including blood pressure (BP) and pulse rate (PR) 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 lb). Exclusion Criteria: Known immunodeficiency disorder, including positive serology for human immunodeficiency virus (HIV) at screening, or a first degree relative with a hereditary immunodeficiency. Infection with hepatitis B or hepatitis C viruses. Participants with selected acute or chronic infections or infection history. Participants have a known present or a history of malignancy other than a successfully treated or excised non metastatic basal cell or squamous cell cancer of the skin. History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Use of tobacco/nicotine containing products within 3 months prior to dosing or positive urine cotinine test.

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

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Period A<br>Single oral dose of 200 mg 14C labeled PF-06651600 containing approximately 300 nCi 14C (ie, radiolabeled PF 06651600). | Drug: 14C-PF-06651600<br>* Oral solution of 200 mg 14C labeled PF-06651600 containing approximately 300 nCi radioactivity<br>|
| Experimental: Period B<br>Single oral dose of 200 milligrams (mg) unlabeled PF-06651600 followed at time of peak plasma concentration (Tmax) by an Intravenous (IV) dose of 60 micrograms.14C -PF-06651600 containing approximately 300 nCi 14C (ie, radiolabeled PF-06651600). | Drug: 14C-PF-06651600 IV<br>* IV solution 60 micrograms of 14C labeled PF-06651600 containing approximately 300 nCi radioactivity<br>Drug: PF-06651600<br>* Oral solution 200mg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mass Balance: Cumulative recovery (%) of radioactivity in urine | Cumulative recovery (%) of radioactivity in urine. | from time zero to the time of last measurable concentration following oral administration of 14C PF-06651600 microtracer dose up to day 24 | 
| Mass Balance: Cumulative recovery (%) of radioactivity in feces | Cumulative recovery (%) of radioactivity in feces | from time zero to the time of last measurable concentration following oral administration of 14C PF-06651600 microtracer dose up to day 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount (% of the administered dose) of major metabolites of PF-06651600 in plasma |  | Hour 0 up to 312 hours post-dose. | 
| Amount (% of the administered dose) of major metabolites of PF-06651600 in urine |  | Hour 0 up to 312 hours post-dose. | 
| Amount (% of the administered dose) of major metabolites of PF-06651600 in feces |  | Hour 0 up to 312 hours post-dose. | 
| Cmax | Maximum plasma concentration | Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose | 
| AUClast | Area under the plasma concentration time profile from time 0 to time of the last quantifiable concentration (Clast) | Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose | 
| AUCinf | Area under the plasma concentration time profile from time 0 to infinity | Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose | 
| Tmax | Time for Cmax | Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose | 
| t1/2 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose | 
| CL (IV) | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). Clearance obtained after intravenous infusion dose (apparent clearance) is influenced by the fraction of the dose absorbed. | Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose | 
| CL/F (oral) | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). Clearance obtained after intravenous infusion dose (apparent clearance) is influenced by the fraction of the dose absorbed. | Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose | 
| Vss | Steady state volume of distribution following IV infusion | Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose | 
| Vz/F | Apparent volume of distribution following oral administration | Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose | 
| Total 14C_Urine_PO | Total radioactivity excreted into the urine from time zero to the time of last measurable concentration following oral administration of 14C PF 06651600 microtracer dose | Pre-dose, Day1, day 2, day 3, day 4, day 5, day 6 and day 7 post-dose | 
| Total 14C_Urine_IV | Total radioactivity excreted into the urine from time zero to the time of last measurable concentration following IV administration of 14C PF 06651600 microtracer dose | Pre-dose, Day1, day 2, day 3, day 4, day 5, day 6 and day 7 post-dose | 
| AE | Number of subjects and number of AEs which are any untoward medical occurrence regardless of attribution to study drug in a participant who received study drug. | Baseline (Day 0) up to 90 days after last dose of study medication | 
| Number of participants with clinically significant changes to the physical examination | clinically significant changes to the physical examination | Baseline (Day 0) up to Day 24 | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Vital signs (temperature, respiratory rate, pulse, systolic and diastolic blood pressure) obtained from each participant. Clinical significance of vital signs was determined at the investigator's discretion. | Baseline (Day 0) up to Day 24 | 
| Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities | Laboratory parameters include: hematological and chemical parameters | Baseline (Day 0) up to Day 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Phase 1, Male, healthy