A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE, 2-PERIOD STUDY IN HEALTHY ADULT MALE PARTICIPANTS TO ASSESS THE MASS BALANCE, ABSOLUTE BIOAVAILABILITY, FRACTION ABSORBED, AND PHARMACOKINETICS OF [14C]PF-06821497 USING A 14C-MICROTRACER APPROACH
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Pfizer
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Metabolic profiling/identification and determination of relative abundance of [14C]PF-06821497 and the metabolites of [14C]PF-06821497 in plasma, urine, and feces
Study Overview
Brief Summary
The purpose of this study is to learn how a certain amount of [14C] PF-06821497 is taken up into the bloodstream and removed from the body.
The study is seeking participants who are:
- Males aged 18 years or older.
- Are confirmed to be healthy after performing some medical and physical tests.
- Weigh more than 50 kilograms and have a body mass index of 16 to 32 kg per meter squared.
The study consists of two parts. In part one, all participants will receive one full dose of [14C]PF-06821497 by mouth. Part two will begin at least 14 days after the dose in part one. In part two participants will receive one full dose of PF-06821497 by mouth and one small dose of [14C]PF-06821497 by intravenous (IV) infusion. IV infusion will be directly injected into the veins.
To understand how the medicine is processed in the body, samples of blood, urine, and feces will be collected after each dose is given. This will help understand:
- How much PF-06821497 is taken up into the bloodstream when taken by mouth compared to the dose given by IV
- How the body removes it from the bloodstream.
Participants will take part in the study for about 11 weeks, including the initial evaluation and follow-up periods.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Male participants aged 18 years at screening who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
- •Body mass index (BMI) of 16-32 kg/m2; and a total body weight of >50kg (110lb)
- •Participants who are willing to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
Exclusion Criteria
- •Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy, prior bariatric surgery, ileal resection, inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease).
- •Chronic liver diseases including alcoholic liver disease, viral hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, Wilson's disease, hemochromatosis, alpha-1 antitrypsin deficiency, human immunodeficiency virus, or other chronic liver disease.
- •Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer). Participation in studies of other investigational products (drug or vaccine) at any time during their participation in this study.
- •Total [14C] radioactivity measured in plasma at screening exceeding 11 mBq/mL
Arms & Interventions
Cohort 1
Participants will receive one dose of [14C] PF-06821497 by mouth in Period 1. After a washout, participants will receive one dose of PF-06821497 by mouth and one intravenous (IV) infusion of [14C] PF-06821497 in Period 2
Intervention: Oral [14C] PF-06821497 (Drug)
Cohort 1
Participants will receive one dose of [14C] PF-06821497 by mouth in Period 1. After a washout, participants will receive one dose of PF-06821497 by mouth and one intravenous (IV) infusion of [14C] PF-06821497 in Period 2
Intervention: Oral PF-06821497 (Drug)
Cohort 1
Participants will receive one dose of [14C] PF-06821497 by mouth in Period 1. After a washout, participants will receive one dose of PF-06821497 by mouth and one intravenous (IV) infusion of [14C] PF-06821497 in Period 2
Intervention: IV [14C] PF-06821497 (Drug)
Outcomes
Primary Outcomes
Metabolic profiling/identification and determination of relative abundance of [14C]PF-06821497 and the metabolites of [14C]PF-06821497 in plasma, urine, and feces
Time Frame: Period 1 pre-dose to maximum Day 14
Amount of metabolites of \[14C\]PF-06821497 in plasma, urine, and feces
Total recovery of radioactivity in urine, feces, and total excreta (urine + feces) as percentage of total radioactive dose administered
Time Frame: Period 1 pre-dose to maximum Day 14
To characterize the extent of excretion of total radioactivity in urine and feces following administration of a single oral dose of \[14C\]PF-06821497
Secondary Outcomes
- AUClast of total radioactivity and PF-06821497 in plasma(Period 1 pre-dose to maximum Day 14)
- Tmax of total radioactivity and PF-06821497 in plasma(Period 1 pre-dose to maximum Day 14)
- CL of [14C]PF-06821497 in plasma(Period 2 pre-dose to maximum Day 5)
- Number of participants with treatment emergent clinically significant abnormal vital measurements(Both cohorts from pre-dose to 28 days post-dose)
- Absolute oral bioavailability (F) of [14C]PF-06821497(Period 2 pre-dose to maximum Day 5)
- Cmax of total radioactivity and PF-06821497 in plasma(Period 1 pre-dose to maximum Day 14)
- AUCinf of total radioactivity and PF-06821497 in plasma(Period 1 pre-dose to maximum Day 14)
- AUCinf of [14C]PF-06821497 in plasma(Period 2 pre-dose to maximum Day 5)
- Number of participants with treatment emergent clinically significant laboratory abnormalities(Both cohorts from pre-dose to 28 days post-dose)
- Number of participants with treatment-emergent adverse events (AEs) or serious adverse events (SAEs)(Both cohorts from pre-dose to 28 days post-dose)
- t½ of [14C]PF-06821497 in plasma(Period 2 pre-dose to maximum Day 5)
- AUClast of [14C]PF-06821497 in plasma(Period 2 pre-dose to maximum Day 5)
- Cmax of [14C]PF-06821497 in plasma(Period 2 pre-dose to maximum Day 5)
- Tmax of [14C]PF-06821497 in plasma(Period 2 pre-dose to maximum Day 5)
- Number of participants with treatment emergent clinically significant abnormal ECG measurements(Both cohorts from pre-dose to 28 days post-dose)
- Fraction of [14C]PF 06821497 dose absorbed (Fa)(Period 1 pre-dose to maximum Day 14; Period 2 pre-IV dose to maximum Day 5)
- t½ of total radioactivity and PF-06821497 in plasma(Period 1 pre-dose to maximum Day 14)
- Vss of [14C]PF-06821497 in plasma(Period 2 pre-dose to maximum Day 5)
- Number of participants with treatment emergent clinically significant abnormal physical examination(Both cohorts from pre-dose to 28 days post-dose)