Single Dose Study With Unlabeled Dose and 14C-labeled Microdose of PF-06700841 in Healthy Male Subjects

Study Overview
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Brief Summary
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An open-label, fixed sequence, 2-period including a single oral dose 60 mg PF-06700841 with 14C-labeled microtracer in 1st period, and a single oral dose of 60 mg unlabeled PF-06700841 followed by intravenous administration of 14C-labeled microdose of PF-06700841 1 hour after oral dose in period 2 to characterize the absorption, disposition, metabolism and excretion of PF-06700841 and evaluate the absolute bioavailability and fraction absorbed in the GI tract

Official Title
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A PHASE 1, OPEN-LABEL, NON-RANDOMIZED, 2-PERIOD, FIXED SEQUENCE STUDY TO INVESTIGATE THE ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION OF [14C-PF-06700841] AND TO ASSESS THE ABSOLUTE BIOAVAILABILITY AND FRACTION ABSORBED OF PF-06700841 IN HEALTHY MALE SUBJECTS USING A 14C-MICROTRACER APPROACH

Conditions
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Healthy Male Subjects

Intervention / Treatment
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* Drug: Oral PF-06700841 containing 14C microtracer
* Drug: Oral unlabeled PF-06700841
* Drug: IV 14C-labeled PF-06700841


Participation Criteria
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Eligibility Criteria
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Exclusion Criteria: Any clinically significant malabsorption condition (eg, gastrectomy, bowel resection). Total 14C radioactivity measured in plasma exceeding 11 mBq/mL History of tuberculosis or active or latent or inadequately treated infection, positive QuantiFERON®-TB Gold test Use of tobacoo/nicotine containing products 3-m prior to dosing or positive urine cotinine test Use of herbal supplements within 28 days prior to the first dose of study medication Use of prescription or nonprescription drugs (including vitamins and dietary supplements) within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication. As an exception, acetaminophen may be used at doses of 1 g/day. Limited use of non-prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case-by-case basis following approval by Pfizer Inability to have at least one bowel movement every 2 days on average eGFR of <90 mL/mim/1.73 m2 based on MDRD equation Have been vaccinated with live or attenuated live vaccine within the 6 weeks prior to the first dose of investigational product, or expects to be vaccinated with these vaccines during study treatment, or within the 6 weeks following the last dose of investigational product.

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
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2-period, fixed sequence<br>fixed sequence with 2 treatment period | Drug: Oral PF-06700841 containing 14C microtracer<br>* Oral dose of 60 mg unlabeled PF-06700841 co-formulated with 30 ug 14C-labeled (300 nCi) PF-06700841 in 1st period<br>Drug: Oral unlabeled PF-06700841<br>* 60 mg unlabeled PF-06700841 oral dose in 2nd period<br>Drug: IV 14C-labeled PF-06700841<br>* 30 ug 14C-labeled (300 nCi) PF-06700841 intravenous infusion over 5 min in 2nd period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mass balance_urine | cumulative recovery of radioactivity over time in urine, as percentage of total radioactive dose administered | hour 0 up to 312 hours post dose | 
| mass balance_feces | cumulative recovery of radioactivity over time in feces, as percentage of total radioactive dose administered | hour 0 up to 312 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| metabolite identification_plasma | metabolic identification and profiling in plasma following a single oral dose of 14C-labeled PF-06700841 | hour 0 up to 312 hours post dose | 
| plasma Cmax for total 14C radioactivity | maximum concentration of total 14C radioactivity in plasma following a single oral dose of 14C-labeled PF-06700841 | hour 0 up to 312 hours post dose | 
| plasma Tmax for total 14C radioactivity | time with highest concentration of radioactivity in plasma following a single oral dose of 14C-labeled PF-06700841 | hour 0 up to 312 hours post dose | 
| plasma AUClast for total 14C radioactivity | area under curve of total 14C radioactivity in plasma from time 0 to tlast following a single oral dose of 14C-labeled PF-06700841 | hour 0 up to 312 hours post dose | 
| plasma AUCinf for total 14C radioactivity | area under curve of total 14C radioactivity in plasma from time 0 to infinite following a single oral dose of 14C-labeled PF-06700841 | hour 0 up to 312 hours post dose | 
| Oral clearance for total 14C radioactivity | oral clearance (CL/F) of total activity following a single oral dose of 14C-labeled PF-06700841 | hour 0 up to 312 hours post dose | 
| plasma half-life for total 14C radioactivity | half-life (t1/2) of total radioactivity in plasma following a single oral dose of 14C-labeled PF-06700841 | hour 0 up to 312 hours post dose | 
| volume of distribution for total 14C radioactivity | apparent volume of distribution (Vz/F) of total radioactivity following a single oral dose of 14C-labeled PF-06700841 | hour 0 up to 312 hours post dose | 
| plasma Cmax for PF-06700841 | maximum concentration of PF-06700841 in plasma following a single oral dose of 14C-labeled or unlabeled PF-06700841 | hour 0 up to 96 hours post dose | 
| plasma Tmax for PF-06700841 | time with highest concentration of PF-06700841 in plasma following a single oral dose of 14C-labeled or unlabeled PF-06700841 | hour 0 up to 96 hours post dose | 
| plasma AUClast for PF-06700841 | area under curve of PF-06700841 in plasma from time 0 to tlast following a single oral dose of 14C-labeled or unlabeled PF-06700841 | hour 0 up to 96 hours post dose | 
| plasma AUCinf for PF-06700841 | area under curve of PF-06700841 in plasma from time 0 to infinite following a single oral dose of 14C-labeled or unlabeled PF-06700841 | hour 0 up to 96 hours post dose | 
| Oral clearance for PF-06700841 | oral clearance (CL/F) of PF-06700841 following a single oral dose of 14C-labeled or unlabeled PF-06700841 | hour 0 up to 96 hours post dose | 
| plasma half-life for PF-06700841 | half-life (t1/2) of PF-06700841 in plasma following a single oral dose of 14C-labeled or unlabeled PF-06700841 | hour 0 up to 96 hours post dose | 
| volume of distribution for PF-06700841 | apparent volume of distribution (Vz/F) of PF-06700841 following a single oral dose of 14C-labeled or unlabeled PF-06700841 | hour 0 up to 96 hours post dose | 
| plasma Cmax for 14C-labeled PF-06700841 | maximum concentration of 14C-labeled PF-06700841 in plasma following a single iv dose of 14C-labeled PF-06700841 | hour 0 up to 96 hours post dose | 
| plasma Tmax for 14C-labeled PF-06700841 | time with highest concentration of 14C-labeled PF-06700841 in plasma following a single iv dose of 14C-labeled PF-06700841 | hour 0 up to 96 hours post dose | 
| plasma AUClast for 14C-labeled PF-06700841 | area under curve of 14C-labeled PF-06700841 in plasma from time 0 to tlast following a single iv dose of 14C-labeled PF-06700841 | hour 0 up to 96 hours post dose | 
| plasma AUCinf for 14C-labeled PF-06700841 | area under curve of 14C-PF-06700841 in plasma from time 0 to infinite following a single iv dose of 14C-labeled PF-06700841 | hour 0 up to 96 hours post dose | 
| clearance for 14C-labeled PF-06700841 | clearance (CL) of 14C-labeled PF-06700841 following a single iv dose of 14C-labeled PF-06700841 | hour 0 up to 96 hours post dose | 
| plasma half-life for 14C-labeled PF-06700841 | half-life (t1/2) of 14C-labeled PF-06700841 in plasma following a single iv dose of 14C-labeled PF-06700841 | hour 0 up to 96 hours post dose | 
| volume of distribution for 14C-labeled PF-06700841 | volume of distribution (Vz/F) of 14C-labeled PF-06700841 following a single iv dose of 14C-labeled PF-06700841 | hour 0 up to 96 hours post dose | 
| unchanged PF-06700841 recovered in urine | percentage of unchanged PF-06700841 recovered in urine (Ae%) following a single oral dose of PF-06700841 | hour 0 up to 96 hours post dose | 
| renal clearance of PF-06700841 | renal clearance (CLr) following a single oral dose of PF-06700841 (Ae%/AUCinf for PF-06700841) | hour 0 up to 96 hours post dose | 
| Bioavailability of oral PF-06700841 | Absolute bioavailability (F) following a single oral dose relative to a single iv dose of PF-06700841 | hour 0 up to 96 hours post dose | 
| Fraction absorbed of oral PF-06700841 | Fraction absorbed in gut (Fa) following oral dose of PF-06700841 | hour 0 up to 144 hours post dose | 
| metabolite identification_urine | metabolic identification and profiling in urine following a single oral dose of 14C-labeled PF-06700841 | hour 0 up to 312 hours post dose | 
| metabolite identification_feces | metabolic identification and profiling in feces following a single oral dose of 14C-labeled PF-06700841 | hour 0 up to 312 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PF-06700841, mass balance, metabolites, absolute bioavailability