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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Male Subjects
• Intervention / Treatment: Drug: Oral PF-06700841 containing 14C microtracer; Drug: Oral unlabeled PF-06700841; Drug: IV 14C-labeled PF-06700841

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • PRA Health Sciences
  • Utrecht, Netherlands, 3584 BL
    • PRA Health Sciences Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2018
• Primary Completion (Actual): February 21, 2019
• Study Completion (Actual): February 21, 2019

Study Registration Dates

• First Submitted: December 6, 2018
• First Submitted That Met QC Criteria: December 6, 2018
• First Posted (Actual): December 10, 2018

Study Record Updates

• Last Update Posted (Actual): March 6, 2019
• Last Update Submitted That Met QC Criteria: March 5, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: PF-06700841; mass balance; metabolites; absolute bioavailability
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; PF-06700841
• Other Study ID Numbers: B7931014; 2018-002403-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes