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. (B7981011)

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: 14C-PF-06651600; Drug: 14C-PF-06651600 IV; Drug: PF-06651600

• 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: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period A; Single oral dose of 200 mg 14C labeled PF-06651600 containing approximately 300 nCi 14C (ie, radiolabeled PF 06651600).	Drug: 14C-PF-06651600; Oral solution of 200 mg 14C labeled PF-06651600 containing approximately 300 nCi radioactivity
Experimental: Period B; 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; IV solution 60 micrograms of 14C labeled PF-06651600 containing approximately 300 nCi radioactivity; Drug: PF-06651600; Oral solution 200mg

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2019
• Primary Completion (Actual): July 5, 2019
• Study Completion (Actual): July 5, 2019

Study Registration Dates

• First Submitted: April 17, 2019
• First Submitted That Met QC Criteria: April 25, 2019
• First Posted (Actual): April 29, 2019

Study Record Updates

• Last Update Posted (Actual): July 24, 2019
• Last Update Submitted That Met QC Criteria: July 23, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Phase 1; Male; healthy
• Other Study ID Numbers: B7981011; 2018-003551-38 (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