A Study to Learn How the Medicine Called [14C] PF-06821497 is Taken up Into and Removed From the Body.

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

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 Overview

• Status: Not yet recruiting
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Oral [14C] PF-06821497; Drug: Oral PF-06821497; Drug: IV [14C] PF-06821497

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

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Key eligibility criteria for this study include, but are not limited to the following:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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

Drug: Oral [14C] PF-06821497; A single oral dose of [14C] PF-06821497 will be administered as an extemporaneous suspension in Period 1; Drug: Oral PF-06821497; A single oral dose of PF-06821497 will be administered as an extemporaneous oral suspension in Period 2; Drug: IV [14C] PF-06821497; A single IV infusion of [14C] PF-06821497 will be administered at the Tmax after administration of the unlabeled oral dose of PF-06821497 in Period 2

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 [14C]PF-06821497	Period 1 pre-dose to maximum Day 14
Metabolic profiling/identification and determination of relative abundance of [14C]PF-06821497 and the metabolites of [14C]PF-06821497 in plasma, urine, and feces	Amount of metabolites of [14C]PF-06821497 in plasma, urine, and feces	Period 1 pre-dose to maximum Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 clinically significant abnormal ECG measurements		Both cohorts from pre-dose to 28 days post-dose
Number of participants with treatment emergent clinically significant abnormal vital measurements		Both cohorts from pre-dose to 28 days post-dose
Number of participants with treatment emergent clinically significant abnormal physical examination		Both cohorts from pre-dose to 28 days post-dose
Absolute oral bioavailability (F) of [14C]PF-06821497	To determine the absolute oral bioavailability (F) of PF-06821497 by comparing AUCinf following administration of a single oral dose of PF-06821497 to a single IV microtracer of [14C]PF 06821497	Period 2 pre-dose to maximum Day 5
Fraction of [14C]PF 06821497 dose absorbed (Fa)	To determine the fraction of the dose absorbed (Fa) following administration of a single oral dose of [14C]PF 06821497 from total urinary radioactivity of [14C]PF 06821497 in Period 1 and IV microtracer microdose administration of [14C]PF 06821497 in Period 2	Period 1 pre-dose to maximum Day 14; Period 2 pre-IV dose to maximum Day 5
AUClast of total radioactivity and PF-06821497 in plasma	To quantify plasma area under the concentration versus time curve (AUClast) of PF-06821497 and total radioactivity following administration of a single oral dose of [14C]PF-06821497.	Period 1 pre-dose to maximum Day 14
Cmax of total radioactivity and PF-06821497 in plasma	To quantify plasma peak concentration (Cmax) of PF-06821497 and total radioactivity following administration of a single oral dose of [14C]PF-06821497.	Period 1 pre-dose to maximum Day 14
Tmax of total radioactivity and PF-06821497 in plasma	To quantify plasma time of peak concentration (Tmax) of PF-06821497 and total radioactivity following administration of a single oral dose of [14C]PF-06821497.	Period 1 pre-dose to maximum Day 14
AUCinf of total radioactivity and PF-06821497 in plasma	If data permits, to quantify plasma area under the concentration versus time curve extrapolated to infinity (AUCinf) of PF-06821497 and total radioactivity following administration of a single oral dose of [14C]PF-06821497.	Period 1 pre-dose to maximum Day 14
t½ of total radioactivity and PF-06821497 in plasma	If data permits, to quantify plasma half-life (t½) of PF-06821497 and total radioactivity following administration of a single oral dose of [14C]PF-06821497.	Period 1 pre-dose to maximum Day 14
AUClast of [14C]PF-06821497 in plasma	To quantify plasma area under the concentration versus time curve (AUClast) of PF-06821497 following administration of a single, IV, microtracer of [14C]PF-06821497.	Period 2 pre-dose to maximum Day 5
Cmax of [14C]PF-06821497 in plasma	To quantify plasma peak concentration (Cmax) of PF-06821497 following administration of a single, IV, microtracer of [14C]PF-06821497.	Period 2 pre-dose to maximum Day 5
Tmax of [14C]PF-06821497 in plasma	To quantify plasma time of peak concentration (Tmax) of PF-06821497 following administration of a single, IV, microtracer of [14C]PF-06821497.	Period 2 pre-dose to maximum Day 5
t½ of [14C]PF-06821497 in plasma	If data permits, to quantify plasma half-life (t½) of PF-06821497 following administration of a single, IV, microtracer of [14C]PF-06821497.	Period 2 pre-dose to maximum Day 5
AUCinf of [14C]PF-06821497 in plasma	If data permits, to quantify plasma area under the concentration versus time curve extrapolated to infinity (AUCinf) of PF-06821497 following administration of a single, IV, microtracer of [14C]PF-06821497.	Period 2 pre-dose to maximum Day 5
CL of [14C]PF-06821497 in plasma	If data permits, to quantify plasma clearance (CL) of PF-06821497 following administration of a single, IV, microtracer of [14C]PF-06821497.	Period 2 pre-dose to maximum Day 5
Vss of [14C]PF-06821497 in plasma	If data permits, to quantify plasma volume of distribution at steady-state (Vss) of PF-06821497 following administration of a single, IV, microtracer of [14C]PF-06821497.	Period 2 pre-dose to maximum Day 5
Number of participants with treatment-emergent adverse events (AEs) or serious adverse events (SAEs)		Both cohorts from pre-dose to 28 days post-dose

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, 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 (Estimated): May 24, 2024
• Primary Completion (Estimated): August 9, 2024
• Study Completion (Estimated): August 9, 2024

Study Registration Dates

• First Submitted: April 12, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Bioavailability; Distribution; Absorption; Metabolism; Elimination; Mass balance; Fraction absorbed; Healthy Males; ADME (Absorption, Distribution, Metabolism, and Excretion); Enhancer of zeste homolog 2 (EZH2) inhibitor
• Other Study ID Numbers: C2321007; 2023-508371-36-00 (Registry Identifier: CTIS (EU))

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