A Study in Healthy Adult Male Participants to Assess Absorption, Distribution, Metabolism and Excretion (ADME) of Radiolabeled PF-06865571.

Study Overview
=================
Brief Summary
-----------------
This study is a Phase 1, open-label, non-randomized, 2-period, fixed-sequence, single-dose study of PF-06865571 in healthy male participants to characterize the ADME properties of [14C]PF-06865571 following oral administration; and to evaluate the absolute oral bioavailability (F) and fraction absorbed (Fa) of PF-06865571 following oral administration of unlabeled PF-06865571 and IV administration of [14C]PF-06865571.

Official Title
-----------------
A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE, 2-PERIOD STUDY IN HEALTHY ADULT MALE PARTICIPANTS TO ASSESS THE EXTENT OF EXCRETION, ABSOLUTE BIOAVAILABILITY, FRACTION ABSORBED, AND PHARMACOKINETICS OF [14C]PF-06865571 USING A 14C-MICROTRACER APPROACH

Conditions
-----------------
Healthy Participants

Intervention / Treatment
-----------------
* Drug: Oral [14C]PF-06865571
* Drug: Oral PF-06865571
* Drug: IV [14C]PF-06865571


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male participants, 18 to 60 years of age, inclusive, at the time of signing the informed consent document. Male participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac tests. Participants who are nonsmoking for at least 3 months at the time of signing the informed consent document. BMI of 17.5 to 30.4 kg/m2, inclusive; and a total body weight >50 kg (110 lb). Exclusion Criteria: Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy). History of irregular bowel movements including irritable bowel syndrome or frequent episodes of diarrhea or constipation, defined by less than 1 bowel movement on average per 2 days, or lactose intolerance. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg,or HCVAb. Hepatitis B vaccination is allowed. History of SARS-CoV-2 PCR or antibody (eg, IgG, IgM, etc) positive result would necessitate accompanying history of asymptomatic state for at least 6 months prior to screening. Use of prescription or nonprescription drugs. Previous administration with an unapproved drug within 60 days preceding the first dose of study intervention used in this study. A positive urine drug test. A positive urine cotinine test. A positive COVID-19 (SARS-CoV-2) PCR test. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 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: Study arm<br>One arm of healthy male participants administered a single oral dose of [14C]PF-06865571; followed by a single dose of unlabeled PF-06865571, and IV administration of [14C]PF-06865571 three hours later. | Drug: Oral [14C]PF-06865571<br>* Oral radiolabeled PF-06865571<br>Drug: Oral PF-06865571<br>* Oral PF-06865571<br>Drug: IV [14C]PF-06865571<br>* IV radiolabeled PF-06865571<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total recovery of radioactivity in urine, feces and total excreta (urine + feces) as percentage of total radioactive dose administered. | To characterize the extent of excretion of total radioactivity in urine and feces following administration of a single oral dose of radiolabeled PF-06865571. | Period 1, Pre-dose to maximum Day 21. | 
| Amount (% of administered dose) of radiolabeled PF-06865571 in plasma. | To determine the amount of radiolabeled PF-06865571 in plasma as the % of the administered dose. | Period 1, Pre-dose to Day 6. | 
| Amount of metabolites of radiolabeled PF-06865571 (% of administered dose) in plasma. | To determine the amount of metabolites of radiolabeled PF-06865571 in plasma as the % of the administered dose. | Period 1, Pre-dose to Day 6. | 
| Amount (% of administered dose) of radiolabeled PF-06865571 in urine. | To determine the amount of radiolabeled PF-06865571 in urine as a % of administered dose. | Period 1, Pre-dose to maximum Day 21. | 
| Amount of metabolites of radiolabeled PF-06865571 (% of administered dose) in urine. | To determine the amount of metabolites of radiolabeled PF-06865571 in urine as a % of administered dose. | Period 1, Pre-dose to maximum Day 21. | 
| Amount (% of administered dose) of radiolabeled PF-06865571 in feces. | To determine the amount of radiolabeled PF-06865571 in feces as a % of administered dose. | Period 1, Pre-dose to maximum Day 21. | 
| Amount of metabolites of radiolabeled PF-06865571 (% of administered dose) in feces. | To determine the amount of metabolites of radiolabeled PF-06865571 in feces as a % of administered dose. | Period 1, Pre-dose to maximum Day 21. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUClast of oral radiolabeled PF-06865571 in plasma | Area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (Clast) of radiolabeled PF-06865571 following administration of a single oral dose of radiolabeled PF-06865571. | Period 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose | 
| Cmax of oral radiolabeled PF-06865571 in plasma | Maximum plasma concentration of radiolabeled PF-06865571 following administration of a single oral dose of radiolabeled PF-06865571. | Period 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose | 
| Tmax of oral radiolabeled PF-06865571 in plasma | Time to Cmax following administration of a single oral dose of radiolabeled PF-06865571. | Period 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose | 
| AUCinf of oral radiolabeled PF-06865571 in plasma (if data permit) | Area under the plasma concentration-time profile from time zero extrapolated to infinite time following administration of a single oral dose of radiolabeled PF-06865571. | Period 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose | 
| t1/2 of oral radiolabeled PF-06865571 in plasma (if data permit) | Terminal elimination half-life following administration of a single oral dose of radiolabeled PF-06865571. | Period 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose | 
| AUClast of radioactivity in plasma | Area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (Clast) of radioactivity following administration of a single oral dose of radiolabeled PF-06865571. | Period 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose | 
| Cmax of radioactivity in plasma | Maximum plasma concentration of radioactivity following administration of a single oral dose of radiolabeled PF-06865571. | Period 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose | 
| Tmax of radioactivity PF-06865571 in plasma | Time to Cmax following administration of a single oral dose of radiolabeled PF-06865571. | Period 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose | 
| AUCinf of radioactivity in plasma (if data permit) | Area under the plasma radioactivity concentration-time profile from time zero extrapolated to infinite time following administration of a single oral dose of radiolabeled PF-06865571. | Period 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose | 
| t1/2 of radioactivity in plasma (if data permit) | Terminal elimination half-life following administration of a single oral dose of radiolabeled PF-06865571. | Period 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose | 
| AUClast of intravenous radiolabeled PF-06865571 in plasma | Area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (Clast) of radiolabeled PF-06865571 following administration of a single intravenous dose of radiolabeled PF-06865571. | Period 2: Pre-dose, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose | 
| Cmax of intravenous radiolabeled PF-06865571 in plasma | Maximum plasma concentration of radiolabeled PF-06865571 following administration of a single intravenous dose of radiolabeled PF-06865571. | Period 2: Pre-dose, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose | 
| Tmax of intravenous radiolabeled PF-06865571 in plasma | Time to Cmax following administration of a single intravenous dose of radiolabeled PF-06865571. | Period 2: Pre-dose, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose | 
| AUCinf of intravenous radiolabeled PF-06865571 in plasma (if data permit) | Area under the plasma concentration-time profile from time zero extrapolated to infinite time following administration of a single intravenous dose of radiolabeled PF-06865571. | Period 2: Pre-dose, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose | 
| t1/2 of intravenous radiolabeled PF-06865571 in plasma (if data permit) | Terminal elimination half-life following administration of a single intravenous dose of radiolabeled PF-06865571. | Period 2: Pre-dose, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose | 
| CL of intravenous radiolabeled PF-06865571 in plasma (if data permit) | Systemic clearance following administration of a single intravenous dose of radiolabeled PF-06865571. | Period 2: Pre-dose, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose | 
| Vss of intravenous radiolabeled PF-06865571 in plasma (if data permit) | Steady-state volume of distribution following administration of a single intravenous dose of radiolabeled PF-06865571. | Period 2: Pre-dose, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose | 
| Absolute oral bioavailability of PF-06865571 | Dose-normalized plasma AUCinf (if data permit, otherwise AUClast) following oral unlabeled PF-06865571 compared to IV microtracer PF-06865571 in Period 2. | Period 2: Pre-dose up to 48 hours post-dose | 
| Fraction of the dose absorbed (Fa) for oral PF-06865571 | Total urinary radioactivity following oral administration of radiolabeled PF-06865571 in Period 1 and IV microtracer administration of PF-06865571 in Period 2. | Pre-dose up to 48 hours post-dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ADME